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AACR 2015: New Subsets of Lung Cancer With KRAS Gene Mutations Identified

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Key Points

  • The biologic heterogeneity of KRAS-mutant tumors has hampered the development of more effective treatment strategies for lung adenocarcinoma with activating mutations in KRAS.
  • Researchers identified three subsets of KRAS-mutant lung cancer—KL, KP, and KC—that demonstrated unique intracellular signaling patterns.
  • KL showed sensitivity to several Hsp90 inhibitors, which may prove helpful for individualized therapy in the future.

Mutations of the KRAS gene are commonly known to lead to cancer. However, deeper understanding of exactly how they do this continues to be explored by cancer researchers. Scientists at The University of Texas MD Anderson Cancer Center have gained further insight about the processes behind KRAS mutations through a study that identified three subsets of lung cancer with mutations in this gene. This line of research has the potential to open up new approaches for treatment of lung adenocarcinoma, the most common form of lung cancer. The data were presented at the AACR Annual Meeting 2015, held April 18 to 22 in Philadelphia (Abstract 968).

Study Details

“The development of more effective treatments for lung adenocarcinoma bearing activating mutations in KRAS has been hampered by the biological heterogeneity of KRAS-mutant tumors,” said John Heymach, MD, PhD, Chair of Thoracic/Head & Neck Medical Oncology. “The molecular underpinnings that drive this process are poorly characterized.”

Dr. Heymach and researchers adopted an integrated approach to the discovery of biologically distinct subsets of KRAS-mutant lung adenocarcinoma and explored their molecular vulnerabilities.

“Our work revealed three major subsets of KRAS-mutant lung adenocarcinoma, which were dominated by co-occurring genetic events, each biologically distinct and susceptible to different therapeutic strategies,” said Ferdinandos Skoulidis, MD, PhD, Instructor of Thoracic/Head & Neck Medical Oncology.

The study used data from The Cancer Genome Atlas and other 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 lung adenocarcinoma. Each of the subsets—KL, KP, and KC—demonstrated unique intracellular signaling patterns. KL in particular showed enhanced sensitivity to several Hsp90 inhibitors, drugs that have shown therapeutic promise. In this case, an Hsp90 inhibitor called ganetespib appeared particularly effective.

The study was supported by the National Institutes of Health (P50 CA070907, R01 CA 155196-01A1, CA016672, and 1R01 CAQ168484-01), The V Foundation For Cancer Research, Ms. Jane A. Ford, the Jeannine T. Rainbolt Advanced Scholars Endowment, the Eric and Pat Bodin Cancer Research Fellowship, and the Uniting Against Lung Cancer Legacy Program for Advances in Lung Cancer Research Program.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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