Charles Swanton, MBBS, PhD, FRCP, FMedSci, FRS
London, United Kingdom
Senior Group Leader, Francis Crick Institute & UCL Cancer Institute
Director, Cancer Research UK Lung Cancer Centre of Excellence
Chair, Personalised Medicine
Consultant Thoracic Oncologist,
Tracking breast cancer evolution and causes of cell-to-cell variability.
For many years, tumors were considered homogenous collections of cells that all harbored the same mutations. Researchers designed target therapies for those mutations, expecting these drugs to eradicate tumors because they would affect every cell. In breast cancer, this strategy is successful in many patients, but one in three breast cancer patients will ultimately experience recurrence or spread of the tumor to other organs (metastasis), because they are resistant to these therapies. This may be caused by tumor heterogeneity, where individual tumor cells can harbor entirely unique mutations from one another, which means targeted therapies cannot eliminate every cancer cell. As tumors grow, they can evolve, developing new mutations and genetic changes that help them grow, hide from the immune system, resist therapies, and metastasize. Studying these evolutionary processes will be vital to developing better therapeutic strategies for patients with difficult-to-treat tumors.
Dr. Swanton and his team are generating an in-depth portrait of the evolution of breast cancer—from the very earliest stages to metastasis—through the Breast TRACERx study. This involves analyzing samples from 250 patients that are taken at diagnosis, through treatment, and the moment of relapse (should they experience it); and 150 patients are sequenced thus far. The team is also exploring the role of replication timing in tumor evolution. When cells divide, they replicate their DNA, but replication does not begin at one end of a chromosome and continue through to the other end. Instead, replication initiates at multiple sites on the chromosome, and each site initiates at a distinct time. This timing can go awry in cancer, and, in laboratory studies, the team revealed a relationship between changes in replication timing and mutational burden in cancer cells. They hypothesize that replication timing alterations may propel tumor heterogeneity, fueling breast cancer adaptation and drug resistance.
The team will continue their work on Breast TRACERx, completing sequencing and initial analysis of the data. In addition, they will expand upon their study of tumor heterogeneity by homing in on individual cells within a tumor. Studying cancer at a single cell level allows cancer cell mutational diversity to be revealed at unprecedented resolution. The team recently developed tools to study changes—including chromosome breaks that are common in cancer—in thousands of individual cells in tumors and will continue this work. And finally, the team is exploring the role of extrachromosomal DNA—extra pieces of DNA that are not associated with chromosomes. They are assessing how extrachromosomal DNA could contribute to supplying additional copies of cancer-promoting genes and feeding into drug resistance in breast cancer.
Charles Swanton completed his MD PhD training in 1999 at the Imperial Cancer Research Fund Laboratories and Cancer Research UK clinician scientist/medical oncology training program in 2008. Dr. Swanton runs the Cancer Evolution and Genome Instability Laboratory at the Francis Crick Institute and combines his research with clinical duties at UCLH, focused on how tumors evolve over space and time. His research focuses on branched evolutionary histories of solid tumors, processes that drive cancer cell-to-cell variation in the form of new cancer mutations or chromosomal instabilities, and the impact of such cancer diversity on effective immune surveillance and clinical outcome.
Dr. Swanton was appointed to several prestigious societies: Fellow of the Royal College of Physicians in April 2011; Fellow of the Academy of Medical Sciences in 2015; Napier Professor in Cancer by the Royal Society in 2016; Cancer Research UK’s Chief Clinician in 2017; and elected Fellow of the Royal Society in 2018.
He has been awarded several prizes including the Stand up to Cancer Translational Cancer Research Prize (2015), Glaxo Smith Kline Biochemical Society Prize (2016), and the San Salvatore Prize for Cancer Research (2017). He has also received several honors; the Ellison-Cliffe Medal; election into the Royal Society of Medicine (2017); the Gordon Hamilton Fairley Medal (2018); and the ESMO Award for Translational Cancer Research (2019).
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