From transcriptional rewiring to therapeutic opportunities: targeting MDM2 amplifications in cancer

Samantha Bevill, PhD
Instructor
Department of Cancer Biology
Dana-Farber Cancer Institute
Department of Pathology
Harvard Medical School
Boston, MA, USA

This conference is hosted by Frédéric Charron, PhD, Director of the Molecular Biology of Neural Development Research Unit.

About this conference
In this seminar, Dr. Bevill will describe how high-level MDM2 amplifications impact the transcriptional regulatory landscape of aggressive tumors. She will demonstrate that these de novo functions, coupled with the extreme intratumoral heterogeneity of MDM2, serve as profound drivers of therapeutic resistance. Building on these mechanistic insights, Dr. Bevill will present a novel therapeutic strategy designed to selectively target tumor populations harboring MDM2 amplifications. Unlike conventional approaches that seek to inhibit MDM2’s oncogenic activity, this strategy co-opts its endogenous E3 ubiquitin ligase function to trigger degradation of essential proteins in tumor cells. The work transforms a mechanism of resistance into a precise therapeutic vulnerability, offering a new direction for tumor-specific therapies.

About Samantha Bevill
Samantha Bevill, PhD, is a pharmacologist specializing in the mechanisms of therapeutic resistance in aggressive cancers. She earned her B.S. in Microbiology from Clemson University and her Ph.D. in Pharmacology from the University of North Carolina at Chapel Hill. Under the mentorship of Dr. Gary Johnson, her doctoral research utilized advanced proteomics and genomics to map compensatory kinase signaling pathways in breast cancer. Currently, as a postdoctoral fellow in Dr. Bradley Bernstein’s laboratory, Dr. Bevill investigates the transcriptional regulatory landscapes of aggressive sarcomas. Her work has uncovered a novel role for MDM2 in driving therapeutic resistance. Dr. Bevill’s most recent work, which is co-advised by Dr. Jun Qi, bridges basic mechanistic discovery and therapeutic application, developing chemical biology strategies to leverage MDM2’s E3 ligase activity for tumor-specific protein degradation.

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