LEBANON, NH - Precision oncology aims to use genetic features of a patient's tumor to tailor anti-cancer therapy. DNA mutations in a drug target have provided a number of therapeutic opportunities; however, there are many cancer types that do not have obvious targetable mutations. A research team at Dartmouth's Norris Cotton Cancer Center led by Todd Miller, PhD, sought to determine whether genetic features could be used to identify novel cancer "subtypes" that span multiple organ sites, and whether this approach could be useful to identify novel treatment strategies.
Miller's team successfully demonstrated that genetic and drug sensitivity data from cancer cells can be used to reveal therapeutic vulnerabilities that transcend cancer lineage. Their results, "A transcriptionally-definable subgroup of triple-negative breast and ovarian cancer samples shows sensitivity to HSP90 inhibition" have recently been published in AACR's Clinical Cancer Research.
"We discovered that a novel, genetically definable mixed subgroup spanning both triple-negative breast cancer and ovarian cancer is vulnerable to treatment with heat shock protein 90 (HSP90) inhibitors," says Miller. "HSP90 inhibitors have been investigated as potential anti-cancer drugs for many years in clinical trials guided by organ site, but tumor response rates have been low. We postulate that testing such drugs in a genetically defined subpopulation of patients would increase response rates."
The team's findings suggest that genetic signatures may be useful to identify cancer subgroups that transcend organ site/lineage and are sensitive to a given class of therapeutics. Future steps include a clinical study using the genetic signature to determine whether it predicts sensitivity to HSP90 inhibitors.
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Todd Miller, PhD, is Co-Director of the Cancer Biology & Therapeutics Research Program and Scientific Director of the Comprehensive Breast Program at Dartmouth's Norris Cotton Cancer Center, and Associate Professor of Molecular and Systems Biology at Dartmouth's Geisel School of Medicine. His research interests include identification of cancer signaling pathways and the development of targeted therapies for breast and other cancers. https://geiselmed.dartmouth.edu/miller/. Twitter: @DartmouthLab.
About Norris Cotton Cancer Center at Dartmouth-Hitchcock
Norris Cotton Cancer Center combines advanced cancer research at Dartmouth's Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center in Lebanon, NH, at Dartmouth-Hitchcock regional locations in Manchester, Nashua and Keene, NH, and St. Johnsbury, VT, and at partner hospitals throughout New Hampshire and Vermont. It is one of 51 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.
Journal
Clinical Cancer Research