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Residual tumor cells are a barrier to targeted cancer therapeutics

(Philadelphia, PA) Over the past five years, so-called molecularly targeted therapies for cancer have held out great promise. These therapies are based on blocking a cancer-causing genetic pathway that has been turned on in a tumor, thereby allowing it to proliferate and grow in an uncontrolled manner. For a small number of cancers, chronic treatment with molecularly targeted therapies has been shown to be effective in the clinic at least in the short-term. Recently, based on animal models, several investigators have proposed that chronic treatment possibly even brief treatment with molecularly targeted therapies might eliminate cancers. Curing cancers with short-term treatment, however, contrasts sharply with clinical experience with cancer patients, say Penn researchers. This suggests that tumors often become resistant to therapy by finding a way around the genetic blockade.

Using a model for breast cancer, researchers in the Abramson Family Cancer Research Institute of the University of Pennsylvania report that after blocking the gene c-MYC, which is commonly overexpressed in human breast cancers, the tumor still persists. Senior author Lewis A. Chodosh, MD, PhD, Associate Professor, Departments of Cancer Biology and Medicine, and colleagues report their findings in the December issue of Cancer Cell.

Specifically, the group found that after turning off c-MYC in a mouse model, 50 percent of c-MYC-induced mammary cancers were still able to grow. They also found that residual cancer cells persisted in all animals even those that were seemingly cancer-free. These residual cells quickly recovered their malignant properties either spontaneously or after the researchers reactivated MYC. Additionally, by sequentially turning the MYC gene on and off in these tumors in order to simulate the treatment of patients with multiple rounds of a molecularly targeted therapy, the investigators found that nearly every tumor eventually progressed to a state that
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
4-Jan-2005


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