Oxford University Oxford, United Kingdom
Emeritus Professor of Medical Oncology Director, Cancer Research UK Medical Oncology Unit
Studying how tumor cells adapt to survive and identifying strategies to block these survival adaptations.
As tumors grow, their need for nutrients and oxygen requires the use of blood vessels and metabolic processes employed by normal cells. Dr. Harris is conducting studies to understand and exploit the methods used by tumors to adapt and survive. His team discovered that tumors co-opt existing blood vessels rather than developing new blood vessels and they are investigating the signaling pathways that regulate this blood vessel growth in breast cancer tumors. Tumor tissues often have a low concentration of oxygen because they rapidly consume oxygen as they grow. They also use much more glucose than normal cells and store it as glycogen for use as an energy source. In laboratory studies, Dr. Harris and his colleagues showed that if the production of glycogen is blocked in cancer cells, they hardly grow but normal cells are less affected. His team is working to develop a new technology that can block glycogen production in cancers, without affecting normal tissues. This targeted strategy may provide a novel form of therapy that is cost-effective, less toxic, and potentially a valuable tool in combination with other existing therapies.
Dr. Harris’ team identified a correlation with a tumors ability to co-opt blood vessels, hypoxic metabolism, and resistance to immunotherapies and are looking for ways to exploit these tumor adaptations to improve the efficacy of immunotherapy in treating breast cancer. In recent studies, they developed SimCells which are derived from bacteria cells but cannot divide and have been rendered non-toxic. They have engineered these cells to express antibodies that recognize HER2-protein and shown that, indeed, about 3000 of these SimCell constructs can bind to each HER2-positive cell. Dr. Harris and his team are capitalizing on the characteristics of SimCells to activate anti-cancer drugs. Researchers have shown that a drug widely used to treat breast cancer is completely inactive until converted to an active form by a specific enzyme. Since this enzyme is generally not present in high quantities in tumors, Dr. Harris has devised a way to modify it to make the enzymes that are present much more active.
Dr. Harris and his colleagues are working to combine the modified and more active enzyme with the previously developed HER2-targeted SimCells. Once perfected, they plan to test the new technology in laboratory models. These studies may result in a novel and affordable technology to target tumors effectively and activate anti-cancer drugs directly at the breast cancer site, increasing the arsenal of tools to treat the disease.
Adrian L. Harris, MD, DPhil is Professor of Medical Oncology at the University of Oxford and Director of the Cancer Research UK Medical Oncology Unit. He is a Consultant Medical Oncologist at the National Health Service, Oxford Radcliffe Hospital Trust, a NIHR Comprehensive Biomedical Research Center designated by Cancer Research as one of three Comprehensive Cancer Centers.
Professor Harris’s research is on tumor angiogenesis, hypoxia and the metabolic response to hypoxia as key targets for anti-cancer therapy. He is interested in understanding the basic biology and science of disease, how this could be applied in development of new treatments and selecting the right patients for the right therapies.
He received his Honors bachelor’s degree in Medicine and Surgery in 1973 at Liverpool University, but undertook an intercalated Biochemistry degree (first class honors) in 1969. He worked at Oxford University from 1975-1978, where he conducted research on mechanisms of resistance to anti-cancer drugs. He then took up a lectureship at the Royal Marsden Hospital where he developed an interest in the endocrine therapy of breast cancer with Professor Ian Smith, and helped develop early aromatase inhibitors.
In 1981 he was appointed Professor of Clinical Oncology at the University of Newcastle Upon Tyne and in 1988 he was invited to Oxford to take up the foundation chair in Medical Oncology and lead the CRUK Molecular Oncology Laboratories at the Weatherall Institute of Molecular Medicine, one of the leading basic science institutes in the United Kingdom.
2008
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