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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
- Seeking new targets to prevent drug resistance and metastasis.
- Ongoing studies are focused on understanding the interplay between environmental (external) and endogenous (internal) factors that promote cancer.
- These efforts may aid the development of new predictive tools to match the right drug to each patient and improve patient outcomes.
As cancers progress, cancer cells acquire genetic mutations that allow them to break the laws governing normal tissue. Within a single tumor, different cells acquire different mutations, creating an intratumor genomic complexity that promotes drug resistance and malignancy. Dr. Swanton is conducting a series of laboratory studies to understand this tumor evolution and identify targets and biomarkers that may improve treatment outcomes for patients with advanced or aggressive cancers.
Full Research Summary
The diversity of genetic changes within breast cancer is 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 occurs during the emergence of drug resistance and that patterns of diversity within breast cancer and other tumor types correlate with poor clinical outcome.
Dr. Swanton's BCRF research is focused on understanding the mechanisms that lead to the generation of tumor diversity and cell-to-cell variation by studying both external (environmental) and internal factors that promote cancer.
Several efforts are ongoing including studies on:
- The effect of cigarette smoke and alcohol consumption on a robust tumor promoting factor called APOBEC3B;
- Circulating mitochondrial DNA as a biomarker of malignancy;
- The effect of aneuploidy—an abnormal number of chromosomes in a cell—on the development of normal and cancer tissues;
- The relationship between intratumor heterogeneity and clinical outcome in metastatic breast cancer.
These efforts may help develop new predictive tools to enable the optimal selection of breast cancer patients for defined therapeutic approaches.
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.
BCRF Investigator Since
The Hamptons Paddle & Party for Pink Award