Titles and Affiliations

Senior Group Leader, Francis Crick Institute & UCL Cancer Institute
Director, Cancer Research UK Lung Cancer Centre of Excellence
Chair, Personalised Medicine
Consultant Thoracic Oncologist
UCLH Hospitals

Research area

Tracking breast cancer evolution and causes of cell-to-cell variability.

Impact

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. 

Progress Thus Far

Our understanding of heterogeneity and evolution derives from pioneering scientists like Dr. Swanton and his team. In lieu of taking a single biopsy from a patient, which only captures one small piece of a tumor, the team took samples from multiple regions of tumors. This strategy, when combined with improved genetic sequencing technologies applied to individual cells, revealed that tumors can be incredibly heterogeneous. 

What’s Next

Dr. Swanton’s team will track the evolution of triple negative breast cancer, an aggressive subtype of breast cancer, from the very earliest stages to metastasis. This study, called Breast TRACERx, will sequence multiple regions of the tumors of 250 patients, and follow the disease from diagnosis throughout primary chemotherapy, to the moment of relapse (should it occur). The team will also explore 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 continuing through to the other end. Instead, replication initiates at multiple sites on the chromosome, and can each site initiates at a distinct time. This timing can go awry in cancer and potentially lead to genetic alterations. This work is all done with the ultimate goal of identifying the evolutionary events that can lead to metastasis and drug resistance and using this information to improve therapies.

Biography

Charles completed his MDPhD training in 1999 at the Imperial Cancer Research Fund Laboratories and Cancer Research UK clinician scientist/medical oncology training in 2008. Charles runs the Cancer Evolution and Genome Instability Laboratory at the Francis Crick Institute and combines his research with clinical duties at UCLH, focussed on how tumours evolve over space and time. Charles researches branched evolutionary histories of solid tumours, 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.

Charles was made Fellow of the Royal College of Physicians in April 2011, appointed Fellow of the Academy of Medical Sciences in 2015, Napier Professor in Cancer by the Royal Society in 2016, appointed Cancer Research UK’s Chief Clinician in 2017, and elected Fellow of the Royal Society in 2018.

Charles has been awarded several prizes including the Stand up to Cancer Translational Cancer Research Prize (2015), Glaxo Smithkline Biochemical Society Prize (2016), San Salvatore prize for Cancer Research (2017) and the Ellison-Cliffe Medal, Royal Society of Medicine (2017), recipient of the Gordon Hamilton Fairley Medal (2018), and the ESMO Award for Translational Cancer Research (2019).

BCRF Investigator Since

2012

Donor Recognition

The Lana Chenko-Haddad Award