Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the fourth-leading cause of cancer-related death in the U.S. Advanced PDAC is extremely hard to treat as it is resistant to chemotherapy and immunotherapy, so there is an urgent need to develop effective treatment approaches against this disease. Different types of cellular stress, including some combinations of drugs, can elicit a cellular program known as senescence, which can cause cancerous cells to stop proliferating and to secrete factors that affect non-cancerous cells present in the tumor, including immune cells.
Dr. Mezzadra and his colleagues found that senescence-inducing drugs led to infiltration of immune cells into PDAC tumors. While these immune cells appear to be suppressed and dysfunctional with respect to their anti-cancer activity, combining senescence-inducing drugs with checkpoint immunotherapies can induce effective immune activity against tumors. Now, he aims to further understand how senescent cells are able to potentiate immunotherapy, which may allow for the design of better therapeutic strategies against pancreatic cancer and hopefully other types of tumors that do not respond to immunotherapy.
Projects and Grants
Understanding the Immunostimulatory Effect of Senescence in Pancreatic Cancer
Memorial Sloan Kettering Cancer Center | Pancreatic Cancer | 2020 | Scott W. Lowe, Ph.D.
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