ABSTRACT

Cancer progresses via an evolutionary process in which subclones with increased fitness can expand and take over less fit clones. Therapy exerts additional pressure on the cancer cells, often resulting in the selection of subclones with unique resistance mechanisms that eventually drive recurrence of the disease. Preventing or delaying the emergence of resistance remains a major medical need and is a highly active topic of research.

In this talk, I will describe different approaches to studying resistance, including studying pre- and post-resistance samples; modeling the dynamics of subclones and estimating their fitness; and comparing frequencies of events in unmatched cohorts of treated and untreated cases. I will describe recent analytical tools (PhylogicNDT) that we have developed for studying tumor heterogeneity, dynamics, and timing of events, which we have applied to discover mechanisms or resistance. In addition, I will demonstrate the power of using cell-free DNA collected before and after treatment, as well as the power of using autopsy samples to uncover the emergence of resistance. Finally, I will discuss the implications of leveraging the heterogeneity of resistance mechanisms to enhance our ability to map these changes, and potentially develop strategies to delay or overcome their emergence.

SPEAKER

Gad Getz is an internationally acclaimed leader in cancer genomics and is pioneering widely used tools for analyzing cancer genomes. Getz is an institute member of the Broad Institute of MIT and Harvard, where he directs the Cancer Genome Computational Analysis Group. Getz is a professor of pathology at Harvard Medical School, and he is a faculty member and director of bioinformatics at the Massachusetts General Hospital (MGH) Cancer Center and Department of Pathology. He is also the inaugural incumbent of the Paul C. Zamecnik Chair in Oncology at the MGH Cancer Center.

HOW TO ATTEND

The seminar will be online using TEAMS. Please register to the seminar. We will send you an invite with the link to the seminar.

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