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Targeted Therapy Shows Promise for Common Form of Lung Cancer

Clinical trials in patients planned (January 31)

A combination of two drugs stopped the growth of the most common genetic subtype of lung cancer in laboratory and animal studies, setting the stage for clinical trials in patients, researchers at Dana-Farber Cancer Institute and other scientists report in a new study.

The study, published in Cancer Discovery, describes a new approach to treatment of lung adenocarcinomas that carry mutations in the gene KRAS, which has defied treatment with targeted therapies. Instead, the authors targeted the genes that carry out KRAS instructions.

“About 30 percent of lung adenocarcinomas have mutations in KRAS,” says the study’s senior author, David Barbie, MD, of the Lowe Center for Thoracic Oncology at Dana-Farber and the Broad Institute of Harvard and MIT. Barbie was studying a pathway KRAS uses to signal other genes that involves TBK1, a protein active in the immune system. He learned that the drug CYT387 (Gilead Sciences)—being tested as a treatment for myelofibrosis—is also active against the TBK1 protein.

Barbie and colleagues tested CYT387 in laboratory samples of lung adenocarcinoma cells and found it to be a potent inhibitor of TBK1 and an effective suppressor of cytokines, proteins that congregate around tumors and help cancer cells survive and spread. Animal studies also produced encouraging results.

Barbie and study co-senior investigator Kwok-Kin Wong, MD, PhD, of the Lowe Center ran tests in more aggressive lung adenocarcinomas that had mutations in KRAS and gene p53. The investigators tested two drugs in tandem against these tumor samples: CYT387 and AZD6244 (AstraZeneca), which inhibits MEK, another downstream protein of KRAS. While neither drug had much effect alone, together they formed a potent combination in laboratory samples and animals. However, Barbie notes that after about eight weeks of treatment, the cancer cells became resistant to the regimen.

Source: Dana-Farber Cancer Institute; January 31, 2014

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