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News about basic science of interest and relevance for cancer clinicians
Thursday, May 26, 2011
Potential Kinase Target Identified for Hormone-Responsive Breast Cancer

Endocrine therapy has improved outcomes for patients with estrogen-receptor positive breast cancer. But not all tumors all tumors respond to existing therapies and other tumors become resistant over time. So potential new targets are always interesting.

 

In an online report in Nature Medicine this week, investigators report that they’ve uncovered a previously unrecognized estrogen receptor regulator. And early evidence suggests it may just be a valuable therapeutic target.

 

The team, led by Georgios Giamas, PhD, Research Associate, and Justin Stebbing, MD, PhD, Professor of Cancer Medicine, at the Imperial College, found that the lemur tyrosine kinase-3 (LMK3) protein regulates estrogen receptor expression and protein stability in breast cancer cell lines.

 

Cell experiments show that LMK3 expression in estrogen-receptor positive breast cancer cell lines increased expression of estrogen-sensitive genes, many of which promote survival and proliferation. By contrast, small inhibitory RNAs that block LMK3 expression had the opposite effect, turning off the estrogen-sensitive genes.

 

When Giamas and colleagues examined breast cancer samples from 613 women, they found that LMK3 expression correlated with disease-free and overall survival, as did two sequence polymorphisms in the gene. Its expression was also associated with response to endocrine therapy, but not with response to cytotoxic adjuvant chemotherapy.

 

Finally, when they used small inhibitory RNAs to block LMK3 expression in established xenograft tumors, tumor growth slowed dramatically. (The xenograft tumors did not shrink, however, which might be cause for caution.)

 

Because LMK3 is a kinase, drug developers should have a relatively easy time finding small molecules that block its activity.

 

Given that fact, and the preclinical data reported in the current paper, I’m guessing we’ll be hearing more about LMK3 in the future.

 

About the Author

Rabiya S. Tuma, PhD
RABIYA S. TUMA, PHD, a Contributing Writer for Oncology Times, is an award winning journalist and a regular contributor to The Economist, and the Journal of the National Cancer Institute. Her work has appeared in a variety of publications including CR Magazine, Yoga + Joyful Living, O The Oprah Magazine, HHMI Bulletin, and the New York Times. Prior to launching her writing career, Rabiya earned her doctorate at the University of Washington and Fred Hutchinson Cancer Research Center and worked at a biotechnology firm in Eugene, Oregon. And though she traded a lab bench for a computer, she remains fascinated with the work that takes basic science into the clinic.

Her OT blog was recognized this year by the American Society of Healthcare Publication Editors (ASHPE) with a bronze award in the category of Best Blog.

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