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Tumor microenvironment helps skin cancer cells resist drug treatment
Date:7/4/2012

uch cancer cells died in the presence of many of these targeted agents, but when grown together with normal cells, cancer cells developed resistance to more than half of the 23 agents tested.

These observations reflect what clinicians often see in patients with cancers such as melanoma. In the case of melanoma, targeted therapies have been developed against a specific, common mutation in a gene known as BRAF. While some patients' tumors show an overwhelming response to BRAF inhibitors and seem to disappear, other patients' tumors only respond by slightly decreasing in size. The failure to shrink tumors at the outset suggests that those tumors possess some level of innate resistance the ability to evade drugs from the beginning of treatment.

"Even though recent advanced in targeted therapy have caused tremendous excitement in melanoma, the fact remains that drug resistance eventually develops in nearly all metastatic melanomas treated with RAF inhibitors, and in some cases is present at the outset of treatment," said Levi A. Garraway, a senior associate member of the Broad Institute, an associate professor at Dana-Farber Cancer Institute and Harvard Medical School. "There are many different types of mechanisms that tumors may hijack to circumvent the effects of therapyno single experimental approach can capture all of these potential mechanisms. Thus, the application of complementary approaches can offer considerable synergy in terms of discovering the full spectrum of clinically relevant resistance mechanisms."

Scientists have uncovered resistance mechanisms that cancer cells develop over time genetic changes in specific genes that may give cancer the ability to overcome the effects of a drug with time but these acquired resistance mechanisms do not explain the innate resistance seen in many tumors.

"We can take cancer cells out of a melanoma patient, put them on a dish, and most times they will turn out to be extremely sensit
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Contact: Haley Bridger
hbridger@broadinstitute.org
617-714-7968
Broad Institute of MIT and Harvard
Source:Eurekalert

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