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Mass. General study reveals how lung cancers evolve in response to targeted treatment
Date:3/23/2011

A detailed analysis of lung tumors that became resistant to targeted therapy drugs has revealed two previously unreported resistance mechanisms. In a report in the March 23 Science Translational Medicine, investigators from the Massachusetts General Hospital (MGH) Cancer Center also describe how the cellular nature of some tumors actually changes in response to treatment and find that resistance-conferring mutations can disappear after treatment is discontinued. The findings support the importance of monitoring the molecular status of tumors throughout the treatment process.

"It is really remarkable how much we oncologists assume about a tumor based on a single biopsy taken at one time, usually the time of diagnosis," says Lecia Sequist, MD, of the MGH Cancer Center, lead author of the report. "Many cancers can evolve in response to exposure to different therapies over time, and we may be blind to the implications of these changes simply because we haven't been looking for them."

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, and in about 12 percent of patients the tumor is driven by a mutation in the epidermal growth factor receptor (EGFR), which stimulates uncontrolled cellular growth. A group of targeted drugs called tyrosine kinase inhibitors (TKIs) block EGFR activity and can halt the growth of tumors driven by such mutations. But in most patients with cancers that respond to TKIs the best known of which are erlotinib (Tarceva) and gefitinib (Iressa) resistance develops after about a year of treatment and tumors resume growing.

Two mechanisms for this resistance have been identified a second EGFR mutation that blocks TKI activity and overproduction of the MET oncogene. There also have been reports of resistant tumors regaining sensitivity to TKIs after a drug-free interval. To better understand the molecular basis for TKI resistance, the research team did a comprehensive ana
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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