Damon Runyon Researchers

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Collin M. Blakely, MD, PhD

Non-small cell lung cancers are frequently driven by specific genetic alterations that can be targeted by precision medicine therapies. However, these therapies often result in only partial responses to treatment, allowing some cancer cells to survive and become fully resistant to therapy.  This ultimately limits patients' long-term survival.  Dr. Blakely focuses on a particular type of lung cancer that is driven by mutations in the EGFR gene. This type of lung cancer frequently develops in younger patients who are non-smokers.  Treatment of this disease with the targeted therapy osimertinib results in partial (incomplete) responses in the vast majority of cases. His goal is to understand why responses to this treatment are almost always incomplete, and to identify new targets for therapies to be used in combination with osimertinib. He will use next-generation sequencing to identify all of the mutations present in patients' tumors in order to understand which ones may be allowing cancer cells to survive EGFR inhibition and will specifically assess the role of alterations in genes that control cellular division. He will also utilize an innovative phase II clinical trial to treat EGFR-mutant lung cancer patients with osimertinib prior to surgery and will use state-of-the-art single cell RNA sequencing technology to understand which factors within cancer cells, or immune cells that infiltrate the tumor, allow for cancer cells to persist.  Ultimately, the goal of this research is to identify novel combination therapy strategies that can improve the depth and duration of response to targeted therapies, allowing patients to live longer.

Project title: "Mechanisms of incomplete response and primary resistance to osimertinib in EGFR-mutant lung cancer"
Institution: University of California, San Francisco
Named Award: Doris Duke-Damon Runyon Clinical Investigator
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Trever G. Bivona, MD, PhD
Cancer Type: Lung
Research Area: Cancer Genetics