Thursday, September 27, 2012
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Cyclin dependent kinase 4 (CDK4);
Ras viral (v-Ras) oncogene (NRAS)
Mouse studies suggest
combined inhibition of CDK4 and MEK could help treat NRAS-mutant melanomas.
In an inducible mouse model of mutant Nras-driven melanoma, gene network
analysis predicted that combined inhibition of CDK4 and MEK would mimic the
loss of mutant NRAS expression. In the same mice, the MEK inhibitor trametinib
and the CDK4 inhibitor PD-0332991
caused greater tumor growth inhibition than either compound alone. Next steps
include evaluating the MEK and CDK4 inhibitor combination in patients with
NRAS-mutant melanomas and identifying additional biomarkers that could help
better determine whether a patient will respond to the combination therapy.
Trametinib, a small molecule inhibitor of MAP kinase
kinase 1 (MAP2K1;
Tobacco Inc. and GlaxoSmithKline
plc, is under review to treat melanoma.
Pharmaceuticals Inc. and Pfizer
Inc. have PD-0332991, an oral small molecule CDK4 and CDK6
inhibitor, in Phase II testing or earlier to treat various cancers.
Published online Sept. 27, 2012
Patent disclosure filed;
available for licensing
Kwong, L.N. et al. Nat.
Med.; published online Sept. 16, 2012;
Contact: Lynda Chin, The University of Texas MD Anderson
Cancer Center, Houston, Texas
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