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Researchers say they’ve identified a promising therapeutic target for multiple myeloma (MM).
The group first discovered that MM patients have higher expression of proline-rich tyrosine kinase 2 (PYK2), a member of the focal adhesion kinase (FAK) family, compared to healthy individuals.
Then, preclinical experiments revealed that PYK2 plays a role in tumor progression, and inhibiting this kinase can impede MM cell growth.
Yu Zhang, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues reported these findings in Blood.
Comparing samples from MM patients and healthy controls, the researchers found that PYK2 is highly expressed in MM. The team even detected higher levels of PYK2 in patients with monoclonal gammopathy of unknown significance and smoldering myeloma.
Additional experiments helped the group elucidate PYK2’s role in MM, showing that the kinase promotes tumor progression by modulating the Wnt/β-catenin signaling pathway.
When the researchers inhibited PYK2, they observed a reduction in MM tumor growth in vivo as well as decreased cell proliferation, cell cycle progression, and adhesion ability in vitro.
In contrast, overexpression of PYK2 promoted the malignant phenotype, as evidenced by enhanced tumor growth and reduced survival in mouse models.
Finally, the researchers showed that a FAK/PYK2 inhibitor, VS-4718, inhibited MM cell growth both in vitro and in vivo.
“In addition to this work recently published by our collaborators at the Dana-Farber Cancer Institute, we have been conducting further research and collaborating with scientific leaders to understand the potential of cancer stem cell inhibitors in hematological malignancies,” said Jonathan Pachter, PhD, head of research at Verastem, Inc., the company developing VS-4781.
“We believe that inhibitors of FAK and PYK2, such as VS-4718, may be useful in the treatment of many types of cancer, particularly where there is minimal residual disease with enrichment of cancer stem cells following chemotherapy. We and our collaborators will be presenting additional research at the upcoming American Society of Hematology in December.”
VS-4718 is being evaluated in a phase 1 dose-escalation trial in patients with advanced solid tumors. Another phase 1 trial in hematological malignancies is set to begin in the first quarter of 2015. 
Researchers say they’ve identified a promising therapeutic target for multiple myeloma (MM).
The group first discovered that MM patients have higher expression of proline-rich tyrosine kinase 2 (PYK2), a member of the focal adhesion kinase (FAK) family, compared to healthy individuals.
Then, preclinical experiments revealed that PYK2 plays a role in tumor progression, and inhibiting this kinase can impede MM cell growth.
Yu Zhang, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues reported these findings in Blood.
Comparing samples from MM patients and healthy controls, the researchers found that PYK2 is highly expressed in MM. The team even detected higher levels of PYK2 in patients with monoclonal gammopathy of unknown significance and smoldering myeloma.
Additional experiments helped the group elucidate PYK2’s role in MM, showing that the kinase promotes tumor progression by modulating the Wnt/β-catenin signaling pathway.
When the researchers inhibited PYK2, they observed a reduction in MM tumor growth in vivo as well as decreased cell proliferation, cell cycle progression, and adhesion ability in vitro.
In contrast, overexpression of PYK2 promoted the malignant phenotype, as evidenced by enhanced tumor growth and reduced survival in mouse models.
Finally, the researchers showed that a FAK/PYK2 inhibitor, VS-4718, inhibited MM cell growth both in vitro and in vivo.
“In addition to this work recently published by our collaborators at the Dana-Farber Cancer Institute, we have been conducting further research and collaborating with scientific leaders to understand the potential of cancer stem cell inhibitors in hematological malignancies,” said Jonathan Pachter, PhD, head of research at Verastem, Inc., the company developing VS-4781.
“We believe that inhibitors of FAK and PYK2, such as VS-4718, may be useful in the treatment of many types of cancer, particularly where there is minimal residual disease with enrichment of cancer stem cells following chemotherapy. We and our collaborators will be presenting additional research at the upcoming American Society of Hematology in December.”
VS-4718 is being evaluated in a phase 1 dose-escalation trial in patients with advanced solid tumors. Another phase 1 trial in hematological malignancies is set to begin in the first quarter of 2015.
Researchers say they’ve identified a promising therapeutic target for multiple myeloma (MM).
The group first discovered that MM patients have higher expression of proline-rich tyrosine kinase 2 (PYK2), a member of the focal adhesion kinase (FAK) family, compared to healthy individuals.
Then, preclinical experiments revealed that PYK2 plays a role in tumor progression, and inhibiting this kinase can impede MM cell growth.
Yu Zhang, PhD, of the Dana-Farber Cancer Institute in Boston, and colleagues reported these findings in Blood.
Comparing samples from MM patients and healthy controls, the researchers found that PYK2 is highly expressed in MM. The team even detected higher levels of PYK2 in patients with monoclonal gammopathy of unknown significance and smoldering myeloma.
Additional experiments helped the group elucidate PYK2’s role in MM, showing that the kinase promotes tumor progression by modulating the Wnt/β-catenin signaling pathway.
When the researchers inhibited PYK2, they observed a reduction in MM tumor growth in vivo as well as decreased cell proliferation, cell cycle progression, and adhesion ability in vitro.
In contrast, overexpression of PYK2 promoted the malignant phenotype, as evidenced by enhanced tumor growth and reduced survival in mouse models.
Finally, the researchers showed that a FAK/PYK2 inhibitor, VS-4718, inhibited MM cell growth both in vitro and in vivo.
“In addition to this work recently published by our collaborators at the Dana-Farber Cancer Institute, we have been conducting further research and collaborating with scientific leaders to understand the potential of cancer stem cell inhibitors in hematological malignancies,” said Jonathan Pachter, PhD, head of research at Verastem, Inc., the company developing VS-4781.
“We believe that inhibitors of FAK and PYK2, such as VS-4718, may be useful in the treatment of many types of cancer, particularly where there is minimal residual disease with enrichment of cancer stem cells following chemotherapy. We and our collaborators will be presenting additional research at the upcoming American Society of Hematology in December.”
VS-4718 is being evaluated in a phase 1 dose-escalation trial in patients with advanced solid tumors. Another phase 1 trial in hematological malignancies is set to begin in the first quarter of 2015.