The Institute of Cancer Research London, United Kingdom
Head of Division of Breast Cancer Research Director of Breast Cancer Now Research Centre Professor of Clinical Oncology and Director of Breast Cancer Now Research Unit, Division of Cancer Studies, King’s College London
Seeking to understand the factors associated with PARP inhibitor resistance and improve outcomes for patients with breast cancer.
In normal cells, DNA damage is recognized and repaired to ensure the genomic integrity of the cell. However, in breast cancer cells with inherited mutations in genes such as BRCA1 or BRCA2, the ability to repair damaged DNA is impaired. This vulnerability in cancer cells has been exploited with treatments, such as PARP inhibitors which block alternative DNA repair processes these tumor cells depend on. Although these drugs are effective, tumor cells can further mutate to restore BRCA function and overcome the lethal effect of the therapy. Dr. Tutt and his team are studying this phenomenon and hope to define steps that can block it, reduce PARP inhibitor resistance, and design new ways to treat these drug-resistant breast cancers.
In laboratory studies, the team has found that the restored BRCA gene produces an abnormal protein that is detectable by the immune system. Similarly, they have seen theprotein in blood from patients. Preliminary findings in patient blood suggest an immune response against tumors with specific [BRCA?] mutations. Studies are ongoing to understand how to harness this to help the immune system fight the resistant tumor. Lastly, Dr. Tutt and others have found that in addition to inherited mutations in BRCA genes, loss of function can also occur through a process called methylation, particularly in triple-negative breast cancers. They have shown that BRCA1 methylation is detectable after surgery and are pursuing another line of research to delve into this finding.
Dr. Tutt and his colleagues are continuing to search for evidence of an anti-tumor response in patient blood with the goal of developing vaccine strategies. They are continuing to study patient tumors in the laboratory to understand the mechanisms of resistance to PARP inhibitor therapy and developing a test for BRCA1 methylation that can be used after chemotherapy and surgery to identify patients who may benefit from PARP inhibitor therapy.
Andrew Tutt, MB, ChB, PhD is a Consultant Clinical Oncologist, Clinical Trialist, Laboratory Team Leader and Director of the breast cancer research teams at The Institute of Cancer Research in London, United Kingdom. He leads a team focused on understanding the fundamental biology and etiology of breast cancer molecular subtypes to inform the discovery and development of new therapeutics and biomarkers.
Dr. Tutt has made seminal contributions to the development of new therapies targeting aberrant DNA damage responses in breast and ovarian cancers. His clinical experience and expertise in basic cancer biology has driven the rapid translation of fundamental discoveries that have resulted in the development and licensing of new drugs and changed guidelines on genetic testing in oncology clinics. He has published a myriad of papers in prestigious journals such as Nature, The New England Journal of Medicine, The Lancet, Nature Medicine, Journal of Clinical Oncology, Annals of Oncology, Cancer Research, Science Translational Medicine and Cancer Discovery. In recognition of his many achievements, Dr. Tutt has been awarded the Fellowship of the Academy of Medical Sciences, the Fellowship of the European Academy of Cancer Sciences, the 2021 ESMO Breast Cancer Award, and the 2022 AACR Team Science Award.
2022
The Estée Lauder Companies' UK & Ireland Award in Honor of Elizabeth Hurley
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