However, study finds letrozole responsiveness can be restored with CDK2 inhibitor roscovitine-- Jeff Muise
Thursday, February 11, 2010 (Last Updated: 02/12/2010)
THURSDAY, Feb. 11 (HealthDay News) -- The overexpression of low-molecular-weight cyclin E (LMW-E) in the tumors of many menopausal women with estrogen-receptor-positive (ER+) breast cancers nullifies the effects of letrozole, an aromatase inhibitor. However, letrozole's effect can be restored by adding the cyclin-dependent kinase 2 (CDK2) inhibitor roscovitine to treatment, according to a study published online Feb. 9 in Clinical Cancer Research.
Said Akli, Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues exposed cultured MCF-7/Ac1 breast cancer cells to normal cyclin E protein or to the LMW-E form of the protein, then administered letrozole and observed inhibitory effects from the LMW-E protein, but not with the normal cyclin E protein. The researchers then administered roscovitine to the letrozole-unresponsive MCF-7/Ac1 cells and observed the results.
While the LMW-E form of the protein rendered the cancer cells resistant to letrozole, the researchers found that treatment with the CDK2 inhibitor roscovitine blocked increased CDK2 in the LMW-E overexpressing cancer cells, and restored letrozole's therapeutic response.
"Roscovitine treatment can reverse intrinsic or acquired resistance to letrozole due to LMW-E expression in breast cancer cells. These data support clinical investigation of CDK2 inhibitor therapy for postmenopausal women with ER+, LMW-E-expressing breast cancer," the authors write.
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