Charles Swanton

Translational Cancer Therapeutics Laboratory

The Swanton laboratory focuses on mechanisms generating cancer genetic diversity and its consequences on clinical outcome. Our group and others, through next generation sequencing studies, have demonstrated that the principles of Darwinian evolution apply to the growth and adaptation of human tumours.

Our group has demonstrated that intratumour heterogeneity, through tumour sampling bias, impacts upon our ability to successfully qualify cancer biomarkers for clinical use. We have also found evidence for extensive parallel evolution in human tumours, with multiple spatially separated subclones acquiring distinct mutations in the same gene, protein complex or signal transduction pathway, suggesting profound constraints to tumour evolution that might be exploited for therapeutic benefit.

Finally, we are building on recent findings from our group that DNA replication stress, genome doubling events and the APOBEC mutational process appear to contribute to intratumour heterogeneity and accelerate cancer evolution, in order to develop deeper insight into how patterns of cancer diversity may be limited for patient benefit.

Through the integration of our work with the UCL Cancer Trials Centre and UCL Cancer Institute, we are recruiting into the TRACERx study to decipher evolutionary processes in non-small cell lung cancer, and the DARWIN (Deciphering Anti tumour Response With INtratumour heterogeneity) trial program aimed at understanding the impact of cancer diversity upon therapeutic outcome and how cancers evolve and adapt to therapy.

Selected publications

Spatial and temporal diversity in genomic instability processes defines lung cancer evolution Elza C. de Bruin, Nicholas McGranahan, Richard Mitter, Max Salm, David C. Wedge, Lucy Yates, Mariam Jamal-Hanjani, Seema Shafi, Nirupa Murugaesu, Andrew J. Rowan, Eva Gronroos, Madiha Anwar Muhammad, Stuart Horswell, Marco Gerlinger, Ignacio Varela, David Jones, John Marshall, Thierry Voet, Peter Van Loo, Doris M Rassl, Robert C Rintoul, Sam M. Janes, Siow-Ming Lee, Martin Forster, Tanya Ahmed, David Lawrence, Mary Falzon, Arrigo Capitanio, Timothy T. Harkins, Clarence C. Lee, Warren Tom, Enock Teefe, Shann-Ching Chen, Sharmin Begum, Adam Rabinowitz, Benjamin Phillimore, Bradley Spencer-Dene, Gordon Stamp, Zoltan Szallasi, Nik Matthews, Aengus Stewart, Peter Campbell, Charles Swanton Science (2014) Oct 10;346(6206):251-6.corresponding author

The genomic architecture and evolution of clear cell renal cell carcinomas defined by multi-region sequencing M Gerlinger, S Horswell, J Larkin, AJ Rowan, M Salm, I Varela, R Fisher, N McGranahan, N Matthews, CR Santos, P Martinez, B Phillimore, S Begum, A Rabinowitz, B Spencer-Dene, S Gulati, P Bates, G Stamp, L Pickering, M Gore, DL Nicol, S Hazell, PA Futreal, A Stewart, C Swanton Nature Genetics (2014) Mar;46(3):225-33 *corresponding author

Tolerance of whole genome doubling propagates chromosomal instability and accelerates cancer genome evolution Sally M Dewhurst & Nicholas McGranahan, Rebecca A Burrell, Andrew J Rowan, Eva Grönroos, David Endesfelder, Tejal Joshi, Dmitri Mouradov, Peter Gibbs, Robyn L. Ward, Nicholas J. Hawkins, Zoltan Szallasi, Oliver M. Sieber & Charles Swanton Cancer Discovery (2014) Feb;4(2):175-85. corresponding author

Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Carcinoma Biomarkers Sakshi Gulati, Paul Bates, Charles Swanton and Marco Gerlinger *Bates and Swanton joint Corresponding Authors European Urology in press (2014)

Replication stress links cancer structural and numerical chromosomal instability Rebecca A. Burrell, Sarah E. McClelland, David Endesfelder, Petra Groth, Marie-Christine Weller, Nadeem Shaikh, Enric Domingo, Nnennaya Kanu, Sally M. Dewhurst, Eva Gronroos, Su Kit Chew, Andrew J. Rowan, Arne Schenk, Michal Sheffer, Michael Howell, Maik Kschischo, Axel Behrens, Thomas Helleday , Jiri Bartek, Ian P. Tomlinson, Charles Swanton corresponding author. (2013) Nature Feb 28;494(7438):492-6.

Parallel evolution of tumor subclones mimics diversity between tumors Pierre Martinez, Nicolai Juul Birkbak, Marco Gerlinger, Nicholas McGranahan, Rebecca Burrell, Andrew Rowan, Tejal Joshi, Rosalie Fisher, James Larkin, Zoltan Szallasi, Charles Swantoncorresponding author (2013) Journal of Pathology Aug;230(4):356-64.

Computation Optimisation of Targeted DNA Sequencing for Cancer Detection Pierre Martinez, Nicholas McGranahan, Nicolai Juul Birkbak, Marco Gerlinger, and Charles Swanton Scientific Reports (2013) Dec 3;3:3309.

Ultra-deep T-cell receptor sequencing reveals the complexity and intratumour heterogeneity of T-cell clones in renal cell carcinomas. Marco Gerlinger, Sergio A. Quezada, Karl S. Peggs, Andrew J.S. Furness, Rosalie Fisher, Teresa Marafioti, Vishvesh H. Shende5, Nicholas McGranahan, Andrew J. Rowan, Steven Hazell, David Hamm, Harlan S. Robins, Lisa Pickering, Martin Gore, David L. Nicol, James Larkin, Charles Swanton corresponding author Journal of Pathology (2013) Dec;231(4):424-32

Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald N, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund A, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Charles Swanton corresponding author. New England Journal of Medicine (2012) Mar 8;366(10):883-92.

Genome-wide RNA Interference Analysis of Renal Carcinoma Survival Regulators Identifies MCT4 as a Warburg Effect Metabolic Target. Marco Gerlinger, Claudio R. Santos, Bradley Spencer-Dene, Pierre Martinez, David Endesfelder, Rebecca A. Burrell1, Marcus Vetter, Ming Jiang, Rebecca Saunders, Gavin Kelly, Nathalie Rioux-Leclercq, Gordon Stamp, Jean Jacques Patard, James Larkin, Michael Howell, Charles Swanton* Journal of Pathology (2012) Jun;227(2):146-56 *corresponding author**

Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer. Roylance R., Endesfelder D., Gorman P., Burrell R.A., Sander J., Tomlinson I., Hanby A.M., Speirs V., Richardson A., Birkbak N., Eklund A.C., Downward J., Kschischo M., Szallasi Z., Swanton C*. Cancer Epidemiol Biomarkers Prev. (2011) Oct;20(10):2183-94. *Corresponding author

Paradoxical Relationship Between Chromosomal Instability and Survival Outcome in Cancer. Birkbak NJ, Eklund AC, Li Q, McClelland SE, Endesfelder D, Tan P, Tan IB, Richardson AL, Szallasi Z, Swanton C (2011) *Joint Corresponding author Cancer Research. May 15;71(10):3447-3452.

Chromosomal Instability Confers Intrinsic Multi-Drug Resistance Alvin J X Lee, David Endesfelder, Andrew J Rowan, Axel Walther, Nicolai J Birkbak, P Andrew Futreal, Julian Downward, Zoltan Szallasi, Ian P M Tomlinson, Maik Kschischo and Charles Swanton* (2011) Cancer Research Mar 1;71(5):1858-70 *Corresponding author.

CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction. Lee A., Roylance R., Sander J., Gorman P., Endesfelder D., Kschischo M., Jones N.P., East P., Nicke B., Spassieva S., Obeid L., Birkbak N., Szalassi Z., Mcknight N.C., Rowan A., Speirs V., Hanby A., Downward J., Swanton C*. Journal of Pathology 2012 Feb;226(3):482-94

Evaluation of an RNA interference screen-derived mitotic and ceramide pathway metagene in paclitaxel-treated primary ER-/PR-/ERBB2-breast cancer: a retrospective analysis of five clinical trials. Juul N., Eklund A., Li Q., Burrell R.A., Valero V., Andreopoulou E., Esteva F.J., Symmans W.F, Desmedt C., Haibe-Kains B., Sotiriou C., Pusztai L., Szallasi Z. and Swanton C. (2010) Lancet Oncology 11(4):358-65 Corresponding author

Charles Swanton

charles.swanton@crick.ac.uk
+44 (0) 20 7269 3463

  • Qualifications and history
  • 1995 PhD, Imperial Cancer Research Fund, UK (this became Cancer Research UK in 2002)
  • 2002 Membership Royal College of Physicians
  • 2004 Established lab at the London Research Institute, Cancer Research UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK