Normalizing the Tumor Microenvironment to Enhance Cancer Treatment

Wednesday Afternoon Lecture Series For more than three decades, Dr. Jain's laboratory research has focused on one challenge: improving the delivery and efficacy of anti-cancer therapies. Working on the hypothesis that the abnormal tumor microenvironment fuels tumor progression and treatment resistance, the Jain laboratory has developed an array of novel imaging technologies and animal models as well as mathematical models to unravel the complex biology of tumors. They demonstrated that the blood and lymphatic vasculature, fibroblasts, immune cells, and the extracellular matrix associated with tumors are abnormal and together create a hostile tumor microenvironment (e.g., hypoxia, high interstitial fluid pressure, high solid stress). These abnormalities fuel malignant properties of a tumor while preventing treatments from reaching and attacking tumor cells. His lab also reengineered the tumor microenvironment to improve treatment outcomes in animal models and in patients. They demonstrated that the judicious use of antiangiogenic agents—originally designed to starve tumors—could transiently “normalize” tumor vasculature, alleviate hypoxia, increase delivery of drugs and anti-tumor immune cells, and improve the outcome of radiation, chemotherapy, and immunotherapy in a number of animal models. In desmoplastic tumors (such as in pancreatic cancer, hepatocellular carcinoma, and certain breast cancers), the extracellular matrix compresses blood vessels and impedes drug ...
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