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Normalizing the tumor microenvironment to enhance cancer treatment

Wednesday, October 22, 2014


Rakesh K. Jain, Ph.D.
A. W. Cook Professor of Tumor Biology and Director, E. L. Steele Laboratory
Massachusetts General Hospital and Harvard Medical School

Dr. Jain is regarded as a pioneer in the field of tumor microenvironment and widely admired for his seminal discoveries in tumor biology, drug delivery, in vivo imaging, bioengineering, and bench-to-bedside translation. He is most celebrated for proposing a new treatment principle—normalization of the microenvironment—for the treatment of malignant and non-malignant diseases characterized by abnormal vessels. This concept has fundamentally changed the thinking of scientists and clinicians about how antiangiogenic agents work. Dr. Jain’s capacity to integrate knowledge from engineering, optics, mathematics, physiology, immunology, and molecular biology is central to his multidisciplinary approach to tumor biology.


For more than three decades, Dr. Jain’s laboratory research has focused on 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 novel imaging technologies and animal models as well as mathematical models to unravel the complex biology of tumors. The researchers 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 the malignant properties of tumors while preventing treatments from reaching and attacking tumor cells.Jain will discuss how his lab reengineers the tumor microenvironment to improve treatment outcomes in animal models and in patients. His lab demonstrated that the judicious use of antiangiogenic agents—originally designed to starve tumors—could “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.

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