Mechanisms of Action and Resistance to CDK4/6 Inhibitors in Breast Cancer
Abstract
CDK4/6 inhibitors combined with endocrine therapy (ET) are mainstay to treat metastatic estrogen receptor (ER) positive patients. Yet, almost 60% develop resistance to CDK4/6inhibition within 2 years of initial treatment. An ongoing clinical challenge has thus been identifying biomarkers of response to predict patients that will either respond or not respond to palbociclib. Further, there is an unmet need to identify actionable targets for patients that have progressed on CDK4/6 blockade regimens. Currently, the only biomarker being used to identify patients for anti-CDK4/6 therapy is estrogen receptor (ER) by IHC. The goal of my study was thus to identify the therapeutic vulnerabilities of CDK4/6 inhibitor resistance cells and identify key markers that can longitudinally correlate with development of resistance. My data suggests that resistance to palbociclib results in a cascade of events initiating with induction of autophagy and senescence, leading to the promotion of senescence-associated secretory phenotype (SASP) that affects surrounding cells and promotes tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1109502
Entities
People
- Nicole M Kettner
Organizations
- University of Texas at Austin