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Charles Swanton, MBBS PhD FRCP FMedSci FRS
Royal Society Napier Professor of Cancer Medicine
The Francis Crick Institute
University College London Hospitals
Goal: To identify novel factors associated with the resistance to targeted therapy in metastatic breast cancer patients.
Impact: Immunotherapy with checkpoint (PD-L1) inhibitors has shown therapeutic benefit in multiple cancer types, the efficacy remains low in breast cancer, however. Dr. Swanton is investigating the factors in the tumor microenvironment that may play a role in tumor response to immunotherapy. His team is conducting studies to identify novel predictors of checkpoint inhibitor response with the goal of improving treatment strategies for patients with advanced or aggressive cancers.
What’s next: Dr. Swanton and his team will examine the tumor microenvironment to decipher those factors that impact the efficacy of immunotherapy or therapeutic resistance as well as to identify those cells that contribute to breast cancer progression.
Clinical studies have suggested that human breast cancer, including triple-negative breast cancer, can be vulnerable to immune surveillance. However, the efficacy of immunotherapies has been relatively poor with disappointing response rates to current immunotherapies, such as immune checkpoint blockade with anti-PD-L1 agents. Dr. Swanton is investigating the factors involved in therapy resistance to develop novel strategies to overcome resistance and improve outcomes for metastatic breast cancer patients.
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: Tumors consist of cancer cells surrounded by a complex microenvironment of tissue and infiltrating cells. This dynamic arena, the tumor microenvironment (TME) is increasingly becoming recognized as a key factor influencing multiple stages of tumor progression. The precise roles played by different components of the TME and their impact on therapeutic resistance is largely unknown. Dr. Swanton and his colleagues are examining the factors in the TME that may influence the response or resistance to immunotherapy to immunotherapy. By understanding the role of these factors, he hopes to develop novel strategies that will improve patient outcomes.
Current investigation: In the coming year Dr. Swanton’s team will conduct studies to elucidate the mechanisms of resistance to immune checkpoint inhibitors and to understand the factors that influence the efficacy of immunotherapy response in triple-negative breast cancer. In addition, his team will examine individual cell types in the TME to determine their contribution to breast cancer progression. He and his colleagues will also determine how tumors become resistant to the HER2-targeted drug, TDM-1. Results of these studies will broaden our knowledge of breast cancer progression, treatment response and resistance to targeted therapy.
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).