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BCRF Grantee Since

2012

Donor Recognition

The Hamptons Paddle & Party for Pink Award

Area(s) of Focus

Charles Swanton, MD, PhD

Chair, Personalized Cancer Medicine
CR-UK Group Leader
Translational Cancer Therapeutics Laboratory
University College London Cancer Institute
London, United Kingdom

Current Research

The diversity of genetic changes within breast cancer is increasingly seen as a feature associated with poor clinical outcome. Intra-tumor heterogeneity (ITH), the existence of multiple subpopulations of tumor cells with distinct genomic profiles, is the consequence of this genetic diversity. Research suggests that ITH may be a contributor to drug resistance and poor clinical outcome. Dr. Swanton’s BCRF research has shown that response to chemotherapy improves with increasing levels of intra-tumor heterogeneity in some estrogen receptor negative (ER-) tumors, suggesting that tumor diversity itself may be targeted for patient benefit. Different alterations within a tumor contribute to this complexity, however, and the identification of regulators that are driving ITH is crucial for the development of personalized medicine to improve breast cancer outcomes. Dr. Swanton’s laboratory utilizes a genomics approach to study ITH during the course of the disease, together with cell biology-based experiments to tease apart the molecular mechanisms contributing to such diversity. By combining both functional and genomic information, they hope to better understand the mechanisms that lead to the intra-tumor heterogeneity as tumors evolve, and they anticipate that such findings will be fundamental in advancing breast cancer treatments.

Bio

The Translational Cancer Therapeutics (TCT) Laboratory is focused on identification of mechanisms of cancer evolution and its impact on drug resistance and patient stratification. Professor Swanton and his colleagues are using parallel clinical trial and integrative functional genomics approaches to develop new predictive tools to enable the optimal stratification of patients for defined therapeutic approaches. Through work aimed at identifying therapeutic approaches to target distinct patterns of genome instability, the TCT laboratory has demonstrated that chromosomal instability in colorectal cancer is initiated through DNA replication stress. The laboratory is now focusing on 1) a greater understanding of the molecular basis of the origins of intratumor heterogeneity, with a principal focus on Structural and Numerical Chromosomal Instability in solid tumors such as breast cancer in order to attempt to limit the acquisition of multi-drug resistance and treatment failure and 2) an in-depth understanding of the prevalence and prognostic impact of intratumor heterogeneity.