Thursday, August 22, 2013
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Cyclin dependent kinase 4 (CDK4); CDK6
In vitro and mouse studies suggest castration-resistant
prostate cancers expressing the F876L androgen receptor (AR)
mutation could be treated with CDK4 inhibitors. The F876L AR mutation renders
cancers resistant to the AR antagonist Xtandi enzalutamide. In an in
vitro model of enzalutamide-resistant prostate cancer, the F876L AR
mutation switched enzalutamide from an AR antagonist to agonist. In mice with
tumors expressing the F876L AR mutant, inhibitors of CDK4 and CDK6 decreased
tumor growth compared with enzalutamide. Ongoing studies include identifying
patients with prostate cancer who could benefit from CDK4 and CDK6
Inc. and Astellas
Pharma Inc. market Xtandi to treat prostate cancer.
Pharmaceuticals Inc. and Pfizer
Inc. have the CDK4 and CDK6 inhibitor palbociclib
in Phase III testing to treat breast cancer.
Lilly and Co.'s LY2835219, a selective dual
inhibitor of CDK4 and CDK6, is in Phase II testing to treat mantle cell
AG and Astex
Pharmaceuticals Inc. have LEE011, a CDK4 and CDK6
inhibitor, in Phase I testing to treat solid tumors.
Published online Aug. 22, 2013
Patent application filed;
available for licensing
Korpal, M. et al. Cancer
Discov.; published online July 10, 2013;
Contact: Manav Korpal, Novartis Institutes for BioMedical
Research, Cambridge, Mass.
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