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AACR Seeks Public Support to Protest Funding Cuts

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ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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Public Support Sought to Protest NIH Funding Cuts

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The AACR is asking its membership – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR's annual meeting. Dr. Retzlaff is managing director of the AACR's Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we've never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It's all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let's not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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The AACR is asking its membership – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.
The AACR is asking its membership – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR's annual meeting. Dr. Retzlaff is managing director of the AACR's Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we've never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It's all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let's not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR's annual meeting. Dr. Retzlaff is managing director of the AACR's Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we've never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It's all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let's not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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AACR Seeks Public Support to Protest Funding Cuts

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ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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AACR Seeks Public Support to Protest Funding Cuts

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ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

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Gene Expression Signatures Predict Erlotinib Sensitivity in NSCLC

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ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

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ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

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epithelial-to-mesenchymal transition genes, five-gene expression signature, erlotinib, non–small cell lung cancer , lung cancer, cancer, endothelial growth factor receptor mutations
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FROM THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH

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Inside the Article

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Major Finding: Disease control at 8 weeks was 83% in patients with one signature vs. 0% in those without it, and 64% vs. 10% in a similar analysis of patients with and without the second signature.

Data Source: A retrospective analysis of data from the BATTLE trial in patients with non–small cell lung cancer.

Disclosures: This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

Gene Expression Signatures Predict Erlotinib Sensitivity in NSCLC

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Gene Expression Signatures Predict Erlotinib Sensitivity in NSCLC

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

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ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

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epithelial-to-mesenchymal transition genes, five-gene expression signature, erlotinib, non–small cell lung cancer , lung cancer, cancer, endothelial growth factor receptor mutations
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FROM THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH

PURLs Copyright

Inside the Article

Vitals

Major Finding: Disease control at 8 weeks was 83% in patients with one signature vs. 0% in those without it, and 64% vs. 10% in a similar analysis of patients with and without the second signature.

Data Source: A retrospective analysis of data from the BATTLE trial in patients with non–small cell lung cancer.

Disclosures: This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

Gene Expression Signatures Predict Erlotinib Sensitivity in NSCLC

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Gene Expression Signatures Predict Erlotinib Sensitivity in NSCLC

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

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ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

ORLANDO – A set of epithelial-to-mesenchymal transition genes and a novel five-gene expression signature appear to predict disease control with erlotinib in refractory non–small cell lung cancer patients whether they have endothelial growth factor receptor mutations or not.

These candidate biomarkers have potentially broad impact, as they could help identify erlotinib (Tarceva) sensitivity in the 88% of patients with wild-type endothelial growth factor receptor (EGFR), Dr. John V. Heymach said at the annual meeting of the American Association for Cancer Research.

Dr. Heymach described the two gene profiles in an update of the phase II Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) 1 trial. They were identified retrospectively from gene expression profiling of pretreatment core needle biopsies in 101 BATTLE trial patients and by studying 54 non–small cell lung cancer lines to find genes involved in the epithelial-to-mesenchymal transition (EMT).

Currently, the treatment benefit of erlotinib – a tyrosine kinase inhibitor that acts on EGFR and is approved for the treatment of non–small cell lung cancer (NSCLC) and pancreatic cancer - can be predicted in only about 12% of patients who have certain mutations and amplifications of EGFR, said Dr. Heymach of the University of Texas M.D. Anderson Cancer Center, Houston.

Previously reported results from the BATTLE 1 trial, which were presented at the 2010 AACR annual meeting, focused on prespecified markers as predictors of response to EGFR inhibition; these updated findings focused on novel gene markers that were not prespecified, but were discovered retrospectively from the biopsies taken as part of the earlier BATTLE trial work.

The investigators found a five-gene expression signature, including Lipocalin-2 (LCN2), NPR3, OGG1, TRIM72, and a gene of unknown function called C5orf23, which was predictive of disease control in patients treated with erlotinib who lacked EGFR mutations. Disease control occurred by 8 weeks in 83% of those with the signature, compared with 0% of patients who lacked the signature (P less than .001).

They also found that LCN2 was involved in the EGFR pathway, and was associated with epithelial-type tumor cells. The findings suggest it is a promising potential target for therapy.

The EMT genes that were found to predict disease control in this study did so by a different measure: Disease control by 8 weeks occurred in 64% of those with cells that were still epithelial type, while disease control occurred in only 10% of those with mesenchymal type (P = .02). A gene called Axl, which is a tyrosine kinase receptor, was found to be associated with mesenchymal-type cells, and could also be a potential therapeutic target, Dr. Heymach said.

The predictive value of both the five-gene expression signature and the EMT signature will be tested prospectively in the upcoming BATTLE II trial, which will also test markers from the P13K-AKT pathway, EGFR signatures, and KRAS mutations. The trial will have four treatment arms, including erlotinib, sorafenib (Nexavar), erlotinib plus an AKT inhibitor, and the AKT inhibitor with an MEK inhibitor.

Dr. Thomas J. Lynch Jr., the discussant following Dr. Heymach’s presentation of his findings during a late-breaking abstract session at the AACR meeting, praised the "mining of data" from the landmark BATTLE 1 trial, which resulted in these findings.

While the finding are important, perhaps their greatest value is in "elucidating new targets in non–small cell lung cancer more than necessarily determining who benefits from marginally active therapy," said Dr. Lynch, director of the Yale Cancer Center and physician-in-chief at Smilow Cancer Hospital at Yale-New Haven (Conn.).

The BATTLE 1 trial, conducted by a team of researchers at M.D. Anderson, is the first completed prospective, adaptively randomized study in heavily pretreated non–small cell lung cancer patients that mandated tumor profiling with real-time core needle biopsies. The results of the trial demonstrate the feasibility of this approach, and create a new paradigm for translational research, and they represent a substantial step toward realizing personalized lung cancer therapy, according to the investigators. The findings are published in the inaugural issue of Cancer Discovery, which debuted at the 2011 AACR conference (Cancer Discovery 2011;1:OF42-9).

This study was funded by the U.S. Department of Defense, the M.D. Anderson and University of Texas Southwestern Lung Cancer Specialized Program in Research Excellence, and M.D. Anderson’s Cancer Center Support Grant from the National Cancer Institute. Dr. Heymach disclosed that he has received research support from AstraZeneca and Bayer, and has served on advisory boards for AstraZeneca, Genentech, and Bayer.

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epithelial-to-mesenchymal transition genes, five-gene expression signature, erlotinib, non–small cell lung cancer , lung cancer, cancer, endothelial growth factor receptor mutations
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At the 1-year anniversary of the Affordable Care Act, the Obama administration is working to remind Americans of the law's value, while opponents are pointing out its flaws.

For details, listen to this week's Policy & Practice Podcast:

At the 1-year anniversary of the Affordable Care Act, the Obama administration is working to remind Americans of the law's value, while opponents are pointing out its flaws.

For details, listen to this week's Policy & Practice Podcast:

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