KRAS gene mutations are commonly known to lead to cancer, and because of this, investigators are fully committed to understanding exactly how this phenomenon occurs. Researchers working at The University of Texas MD Anderson Cancer Center have identified the processes behind KRAS mutations thanks to a study that managed to identify three subsets of lung cancer with mutations in this specific gene. These new results might have the potential to lead to new approaches for the treatment of lung adenocarcinoma (LUAC), the most frequent form of lung cancer. The data from the study was reported on April 19 during the 2015 American Association for Cancer Research (AACR) Annual Meeting, in Philadelphia.
“The development of more effective treatments for LUAC-bearing activating mutations in KRAS has been hampered by the biological heterogeneity of KRAS-mutant tumors. The molecular underpinnings that drive this process are poorly characterized,”said John Heymach, the chair of Thoracic/Head & Neck Medical Oncology.
Dr. Heymach and his research team used an integrated approach to discover biologically different subsets of KRAS-mutant LUAC and assess their molecular vulnerabilities. “Our work revealed three major subsets of KRAS-mutant LUAC, which were dominated by co-occurring genetic events, each biologically distinct and susceptible to different therapeutic strategies,” explained Ferdinandos Skoulidis expert in Thoracic/Head & Neck Medical Oncology.
The team used data from The Cancer Genome Atlas and other different sources including the MD Anderson-led trial, Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) to identify three robust subsets of KRAS-mutant LUAC. Each one of the identified subsets, KP, KL, and KC, demonstrated exquisite intracellular patterns of signaling. KL showed enhanced sensitivity to some Hsp90 inhibitors, drugs that have revealed therapeutic potential. In particular, an Hsp90 inhibitor named ganetespib seemed especially effective.
The University of Texas MD Anderson Cancer Center is one of only 41 institutions designated by the National Cancer Institute (NCI) as a comprehensive cancer center. For the past 25 years, MD Anderson was ranked as one of the nation’s top two cancer centers in U.S. News & World Report’s annual “Best Hospitals” survey.
This study received funding from the National Institutes of Health, Ms. Jane A. Ford, The V Foundation For Cancer Research, the Eric and Pat Bodin Cancer Research Fellowship, the Jeannine T. Rainbolt Advanced Scholars Endowment and the Uniting Against Lung Cancer Legacy Program for Advances in Lung Cancer Research Program.