New Subsets and Therapeutic Vulnerabilities of Lung Cancer Discovered

A novel study recently provided new insights into the molecular nature of a subtype of lung cancer, adenocarcinoma. There are basically two types of gene mutations in normal cells that can ultimately lead to cancer. While some must be deactivated, like those playing a role in regulating cell cycle or programmed cell death (the so-called tumor suppressor genes), others must be super-activated, like those playing a role in cell proliferation, the oncogenes.

KRAS is an oncogene commonly mutated and implicated in cancer, but scientists continue to study its interactions with cell signals in the hopes of finding new therapeutic approaches to cancer. A team of researchers from The University of Texas MD Anderson Cancer Center led by Professor John Heymach, senior author and chair of Thoracic/Head & Neck Medical Oncology, identified new subsets of KRAS mutations in lung adenocarcinoma and explored their vulnerability to molecular treatments. The study was presented on April 19th during the 2015 American Association for Cancer Research (AACR) Annual Meeting in Philadelphia.

Researchers used an integrated approach to find these biologically distinct subsets in 192 samples of KRAS-mutated lung adenocarcinoma using data from The Cancer Genome Atlas and other sources including the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) trial. Three new cell subsets were found, each with its unique cellular signals and therapeutic sensitivity. One of the subsets, showed particular sensitivity to ganetespib, a drug already in advanced stage of research with a clinical trial for lung cancer starting within a few months.

As noted above, the molecular background of lung adenocarcinoma with KRAS activating mutations is poorly understood and its heterogeneity impairs the development of more effective treatment strategies. This and other research outcomes are offering promising strategies for a future with more directed molecular therapies for lung cancer associated with less adverse effects.

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