Thursday, July 17, 2014
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B cell lymphoma
B cell lymphoma 2
dependent kinase 4 (CDK4);
dependent kinase inhibitor 2A (CDKN2A;
Patient and mouse studies
suggest combined inhibition of CDK4 and BCL2 could help treat high-risk
follicular lymphomas with mutations in the retinoblastoma pathway. In
patients with indolent follicular lymphoma, genomic alterations in members of
the retinoblastoma pathway including CDKN2A, CDKN2B, RB1
and CDK4 were associated with high-risk disease. In mouse xenograft
models of follicular lymphoma with elevated RB1 phosphorylation, a
combination of small molecule inhibitors of CDK4 and BCL2 decreased tumor growth
compared with either inhibitor alone. Next steps could include evaluating the
combination in additional types of
B cell lymphomas with mutations in the retinoblastoma pathway.
Inc. and Amgen
Inc. have the oral small molecule CDK4 and CDK6
in Phase III testing to treat breast cancer.
AG and Otsuka
Pharmaceutical Co. Ltd. have the CDK4 and CDK6 inhibitor LEE011
Phase III testing for the same indication.
At least two other companies have dual inhibitors of CDK4 and CDK6 in Phase
II or earlier testing to treat various cancers.
At least 12 companies have BCL2 inhibitors in
Phase II or earlier testing to treat various cancers.
Published online July 17, 2014
Patent and licensing status
Oricchio, E. et al. J.
Exp. Med.; published online June 9, 2014;
Contact: Hans-Guido Wendel, Memorial Sloan-Kettering Cancer
Center, New York, N.Y.
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