Titles and Affiliations
Emeritus Professor of Medical Oncology
Director, Cancer Research UK Medical Oncology Unit
Research area
Studying how tumor cells adapt to survive and identifying strategies to block these survival adaptations.
Impact
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.
Progress Thus Far
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 what they call miniSimCells 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 miniSimCell constructs can bind to and selectively kill each HER2-positive breast cancer cell. They also show activity in micro-metastases in laboratory models. Dr. Harris and his team are also capitalizing on the characteristics of miniSimCells to activate anti-cancer drugs providing a vehicle for delivering drug activating enzymes directly to the tumor. They team have developed a protocol to mass produce miniSimCells, genetically engineering them to both target HER2 and activate anti-cancer drugs.
What’s next
Dr. Harris and his colleagues will continue to test the novel miniSimCells technology in more complex 3D laboratory models. They will also test combination therapies, specifically miniSimcells plus anti-cancer drugs and other systemic treatments. Other studies will include PARP inhibitors to determine if this addition increases breast cancer cell killing. 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.
Biography
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.
