Description:

Athanasios Vasilopoulos, PhD
Assistant Professor of Radiation Oncology
Northwestern University Feinberg School of Medicine

Undoubtedly, the use of CDK4/6 inhibitors with endocrine therapy has changed the treatment landscape of breast cancer patients with advanced/metastatic ER-positive/HER2-negative disease, thereby establishing a novel treatment standard not only in pretreated patients but also in the first-line setting. Despite the significant progress, several key challenges in the clinic still remain. 1) Which patients will derive the largest benefit? 2) How can we increase response rates to CDK4/6 inhibition (CDK4/6i)? 3) How can we intervene in order to delay or reverse treatment resistance? Here, we provide evidence for a newly identified gene-treatment interaction, based on which SIRT3, through maintaining mitochondrial homeostasis, regulates cellular adaptation to CDK4/6i and duration of response. Our research efforts focus on uncovering underlying mechanisms and evaluating the predictive value of SIRT3 expression/activity for efficacy in response to CDK4/6i. Our ongoing work can have a significant impact on ER+ breast cancer patients through paving the path to novel strategies for exceptional response to CDK4/6 inhibitors and establishing molecular biomarkers for better patient stratification.