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Low forms of cyclin E reduce breast cancer drug's effectiveness
Date:2/9/2010

HOUSTON - Overexpression of low-molecular-weight (LMW-E) forms of the protein cyclin E renders the aromatase inhibitor letrozole ineffective among women with estrogen-receptor-positive (ER+) breast cancers, researchers from The University of Texas M. D. Anderson Cancer Center report in Clinical Cancer Research.

The M. D. Anderson research, led by Khandan Keyomarsi, Ph.D., professor in M. D. Anderson's Department of Experimental Radiation Oncology and the Hubert L. and Olive Stringer Professor in Medical Oncology, found evidence that women whose cancers express the LMW-E are more likely to develop resistance to letrozole. However, their research also showed that treating breast cancer cells with a cyclin-dependent kinase 2 (CDK2) inhibitor can reverse letrozole resistance.

Cyclin E is one of the proteins that regulates the cell cycle, influencing how rapidly a cell passes through the four phases and divides. In tumor cells, cyclin E is converted to low-molecular weight forms, an event that does not occur in normal cells. High levels of LMW-E accelerate the cell's transition through the G1phase, an important checkpoint that can arrest the cell cycle if DNA damage is detected. Elevated levels of LMW-E have been linked to uncontrolled cell proliferation and a poor outcome in breast cancer patients.

Outwitting Drug Resistance

Keyomarsi estimated that approximately 70 percent of all breast cancer patients are estrogen receptor positive (ER+), of which a large percentage are post-menopausal, and would thereby be a candidate to receive an aromatase inhibitor as maintenance therapy. Aromatase inhibitors can reduce the risk of early metastasis among postmenopausal women with ER+ breast cancer. However, not every patient responds to aromatase inhibitors, and those who do will develop resistance to the drugs over time, explained Keyomarsi. Understanding the mechanisms behind this resistance has been a long-standing goa
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Contact: Laura Sussman
lsussman@mdanderson.org
713-745-2457
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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