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Charles Swanton, MD, PhD

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

Current Research

Goal: To identify new methods of preventing drug resistance and metastasis.

Impact: Dr. Swanton is conducting a series of laboratory studies to understand how tumors evolve in order to understand how they become resistant to targeted treatment. His work may lead to new strategies for improving outcomes for patients with advanced or aggressive cancers. 

What’s next: He and his colleagues will investigate the role certain chromosomal and genetic abnormalities play in breast cancer progression and how they affect patient outcomes.

One of the major challenges researchers face in developing new drugs for breast cancer is a phenomenon called intratumor heterogeneity. This means that within a tumor, there are regions that have different genomic features. Intratumor heterogeneity is thought to be an underlying cause of drug resistance because not all the cancer cells within the tumor may respond to a particular form of therapy. Dr. Swanton is investigating how cancer cells acquire such a variety of mutations as the disease develops, which he hopes will reveal new ways to treat breast cancer more effectively.

Full Research Summary

Research area: Understanding the molecular evolution of breast cancer to identify strategies to reduce drug resistance and improve outcomes of breast cancer patients.

Impact: Cancer is a disease of DNA that is damaged and therefore sends erroneous signals to the cell’s protein-making machinery. Genome instability results when cells that harbor DNA damage pass that damage onto daughter cells during cell division. This makes the daughter cells inherently susceptible to more DNA damage. As this cycle progresses, tumors evolve to become masses of cells with distinctive genomic profiles – a characteristic referred to as intratumor heterogeneity. Intratumor heterogeneity is associated with more aggressive disease and drug resistance, thereby contributing to the failure of new therapies to deliver meaningful outcomes for patients. Dr. Swanton’s research aims to understand this process with the goal of developing strategies that will improve patient outcomes by preventing drug resistance.

Current investigation: Dr. Swanton’s laboratory is conducting studies to gain a greater understanding of the molecular basis of the origins of intratumor heterogeneity that will inform strategies to prevent multi-drug resistance and treatment failure.

What he’s learned so far: In work leading up to the current study, Dr. Swanton and colleagues examined the genomic landscape and intratumor heterogeneity of breast cancer and refocused their work to gain a greater understanding of clinical outcome in metastatic breast cancer. His previous BCRF-supported research has led to a deeper understanding of the relationship between environmental exposures such as cigarette smoke and breast cancer.

What’s next: Dr. Swanton’s team will focus on various genomic alterations leading to tumor heterogeneity and breast cancer evolution. Additionally, they will pursue studies to elucidate the mechanisms of resistance to targeted therapies including immune checkpoint inhibitors and CDK4/6 inhibitors.  He and his colleagues hope that the results of their studies will help to better identify patients that will benefit from immunotherapy, determine why some patients develop resistance to therapy, and thus further the understanding of breast cancer progression and treatment response.

Biography

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.

Large Researcher Headshot - Swanton Charles

BCRF Investigator Since

2012

Donor Recognition

The Hamptons Paddle & Party for Pink Award

Area(s) of Focus