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Research conducted in mice suggests that genomic screening might reveal cancer patients who are likely to develop treatment-related anemia.
The study showed that mice lacking Pten and Shp2—enzymes targeted by certain anticancer therapies—can’t produce and sustain enough red blood cells.
Investigators said this helps explain why anemia is a common side effect of anticancer drugs that target enzymes involved in tumor growth.
“Based on this unexpected finding, we might want to think about screening cancer patients’ genetic backgrounds for loss of Pten or Pten-regulated signals before prescribing anticancer drugs that might do more harm than good,” said Gen-Sheng Feng, PhD, of the University of California San Diego School of Medicine.
Dr Feng and his colleagues described their research in PNAS.
First, the team genetically engineered mice to lack Pten, Shp2, or both enzymes. The Pten-deficient mice had elevated white blood cells counts, consistent with myeloproliferative neoplasms (MPNs).
The Shp2-deficient mice experienced the opposite—lower white blood cell counts. And mice lacking both Pten and Shp2 had relatively normal white blood cell counts, suggesting that loss of Shp2 suppresses MPNs induced by Pten loss.
However, the investigators also discovered that mice lacking both enzymes had shorter lifespans than wild-type mice or mice lacking 1 of the enzymes.
This was because the combined deficiency of Shp2 and Pten induced lethal anemia. And this anemia was a result of 2 factors: red blood cells failed to develop properly and those that did form had a shortened lifespan.
To build upon these findings, the investigators treated Pten-deficient mice with the Shp2 inhibitor 11a-1 or with the MEK inhibitor trametinib. (MEK belongs to the same cellular communication network as Shp2.)
As with genetic deletion of Shp2, pharmacologic inhibition of Shp2 suppressed MPN induced by Pten loss and induced severe anemia in the mice.
Trametinib treatment had a similar effect, inducing anemia in Pten-deficient mice but not wild-type mice.
“What we’ve learned is that even if we know a lot about how individual molecules function in a cell, designing effective therapeutics that target them will require a more comprehensive understanding of the cross-talk between molecules in a particular cell type and in the context of disease,” Dr Feng concluded. 
Research conducted in mice suggests that genomic screening might reveal cancer patients who are likely to develop treatment-related anemia.
The study showed that mice lacking Pten and Shp2—enzymes targeted by certain anticancer therapies—can’t produce and sustain enough red blood cells.
Investigators said this helps explain why anemia is a common side effect of anticancer drugs that target enzymes involved in tumor growth.
“Based on this unexpected finding, we might want to think about screening cancer patients’ genetic backgrounds for loss of Pten or Pten-regulated signals before prescribing anticancer drugs that might do more harm than good,” said Gen-Sheng Feng, PhD, of the University of California San Diego School of Medicine.
Dr Feng and his colleagues described their research in PNAS.
First, the team genetically engineered mice to lack Pten, Shp2, or both enzymes. The Pten-deficient mice had elevated white blood cells counts, consistent with myeloproliferative neoplasms (MPNs).
The Shp2-deficient mice experienced the opposite—lower white blood cell counts. And mice lacking both Pten and Shp2 had relatively normal white blood cell counts, suggesting that loss of Shp2 suppresses MPNs induced by Pten loss.
However, the investigators also discovered that mice lacking both enzymes had shorter lifespans than wild-type mice or mice lacking 1 of the enzymes.
This was because the combined deficiency of Shp2 and Pten induced lethal anemia. And this anemia was a result of 2 factors: red blood cells failed to develop properly and those that did form had a shortened lifespan.
To build upon these findings, the investigators treated Pten-deficient mice with the Shp2 inhibitor 11a-1 or with the MEK inhibitor trametinib. (MEK belongs to the same cellular communication network as Shp2.)
As with genetic deletion of Shp2, pharmacologic inhibition of Shp2 suppressed MPN induced by Pten loss and induced severe anemia in the mice.
Trametinib treatment had a similar effect, inducing anemia in Pten-deficient mice but not wild-type mice.
“What we’ve learned is that even if we know a lot about how individual molecules function in a cell, designing effective therapeutics that target them will require a more comprehensive understanding of the cross-talk between molecules in a particular cell type and in the context of disease,” Dr Feng concluded.
Research conducted in mice suggests that genomic screening might reveal cancer patients who are likely to develop treatment-related anemia.
The study showed that mice lacking Pten and Shp2—enzymes targeted by certain anticancer therapies—can’t produce and sustain enough red blood cells.
Investigators said this helps explain why anemia is a common side effect of anticancer drugs that target enzymes involved in tumor growth.
“Based on this unexpected finding, we might want to think about screening cancer patients’ genetic backgrounds for loss of Pten or Pten-regulated signals before prescribing anticancer drugs that might do more harm than good,” said Gen-Sheng Feng, PhD, of the University of California San Diego School of Medicine.
Dr Feng and his colleagues described their research in PNAS.
First, the team genetically engineered mice to lack Pten, Shp2, or both enzymes. The Pten-deficient mice had elevated white blood cells counts, consistent with myeloproliferative neoplasms (MPNs).
The Shp2-deficient mice experienced the opposite—lower white blood cell counts. And mice lacking both Pten and Shp2 had relatively normal white blood cell counts, suggesting that loss of Shp2 suppresses MPNs induced by Pten loss.
However, the investigators also discovered that mice lacking both enzymes had shorter lifespans than wild-type mice or mice lacking 1 of the enzymes.
This was because the combined deficiency of Shp2 and Pten induced lethal anemia. And this anemia was a result of 2 factors: red blood cells failed to develop properly and those that did form had a shortened lifespan.
To build upon these findings, the investigators treated Pten-deficient mice with the Shp2 inhibitor 11a-1 or with the MEK inhibitor trametinib. (MEK belongs to the same cellular communication network as Shp2.)
As with genetic deletion of Shp2, pharmacologic inhibition of Shp2 suppressed MPN induced by Pten loss and induced severe anemia in the mice.
Trametinib treatment had a similar effect, inducing anemia in Pten-deficient mice but not wild-type mice.
“What we’ve learned is that even if we know a lot about how individual molecules function in a cell, designing effective therapeutics that target them will require a more comprehensive understanding of the cross-talk between molecules in a particular cell type and in the context of disease,” Dr Feng concluded.