TO BETTER UNDERSTAND the causes of resistance to treatment in estrogen receptor–positive breast cancer, the Department of Defense has awarded researchers at Baylor College of Medicine multiple grants to study gene anomalies in estrogen receptor–positive breast cancer that are associated with recurrence and poor outcomes as well as developing combinatorial strategies using proteogenomic approaches to targeting HER2-activating mutations in estrogen receptor–positive metastatic breast cancers.
Megha Shyam Kavuri, PhD
Through the Department of Defense Breakthrough Level 2 grant, Megha Shyam Kavuri, PhD, Assistant Professor in the Lester and Sue Smith Breast Center, part of the National Cancer Institute–designated Dan L Duncan Comprehensive Cancer Center at Baylor College, and colleagues will aim to address the mechanistic basis of how poor-prognosis DDR1 overexpression and mutations affect endocrine therapy resistance, tumor growth, and metastasizes using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9-mediated synthetic genetic screens.
WITH THE Breakthrough Level 3 grant, Dr. Kavuri and colleagues will be using estrogen receptor–positive and HER2-mutant patient-derived xenografts to design combinatorial strategies using proteogenomic approaches. In addition, the research team will conduct a phase II clinical trial of neratinib (Nerlynx) in combination with fulvestrant (Faslodex) in estrogen receptor–positive, HER2-mutated metastatic breast cancer to assess the clinical activity of this combination.
Svasti Haricharan, PhD
Research funded through a Department of Defense Breakthrough Level 1 grant, led by Svasti Haricharan, PhD, as the initiating principal investigator, along with Dr. Kavuri, aims to uncover a novel relationship between DNA damage–repair pathways and the activation of a growth receptor in estrogen receptor–positive breast cancer. ■