Description:

The Department of Biochemistry & Molecular Genetics presents:

Matthew G. Oser MD, PhD
Department of Medical Oncology, Division of Molecular and Cellular Oncology
Assistant Professor, Dana-Farber Cancer Institute,
Harvard Medical School

Presentation: 

Innovative Therapeutic Strategies for Small Cell Lung Cancer: From Genomic Vulnerabilities to Lineage Plasticity

Small cell lung cancer (SCLC) is characterized by near-universal loss of RB1 and TP53 and by molecular subtypes driven by lineage transcription factors, yet effective therapeutic strategies remain limited. In this talk, I will highlight three examples from my lab where CRISPR-based functional genomics has uncovered new therapeutic opportunities in SCLC. First, I will discuss the discovery of cyclin A/B RxL inhibition as a novel therapeutic strategy that exploits the core genomic vulnerability created by RB1 and TP53 loss in SCLC, with broader applicability to cancers harboring mutations that compromise the G1-S checkpoint. Second, I will describe how the use of endogenous knock-in reporters of lineage transcription factor dependencies in SCLC, coupled with genome-wide CRISPR screening, can reveal novel potential therapeutic strategies. Third, I will present how CRISPR-based somatic gene editing in mouse models of SCLC identified EED, as part of the PRC2 complex, as essential to maintain the SCLC neuroendocrine tumor cell state, thereby revealing EED as a potential therapeutic target to block lung adenocarcinoma-to-SCLC transformation, a mechanism of acquired resistance to targeted therapies in lung adenocarcinoma. Together, these examples showcase how targeting genomic vulnerabilities, lineage transcription factor dependencies, and lineage plasticity can open new avenues for precision therapy in SCLC.

Host: Dr. Lu Wang, Assistant Professor, Biochemistry and Molecular Genetics

Refreshments will be served.