Noopur Raje, MD
Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center
Associate Professor of Medicine
Harvard Medical School
Our laboratory focuses on 2 major areas:
Multiple Myeloma Biology and Therapeutics
The bone marrow microenvironment plays a crucial role in multiple myeloma pathogenesis. Specifically, growth advantage, survival, drug resistance of myeloma cells are modulated by various subsets of bone marrow components including stromal cells, osteoclasts, osteoblasts, and vascular endothelial cells. Recognition and understanding of the biologic significance of this tumor cell microenvironment interaction with a focus of this interaction as a potential target for novel therapeutics is the focus of our studies. Based on preclinical validation several clinical studies to target these interactions are underway. Specifically, we have studied the combination of mTOR inhibitors with lenalidomide as a way of overcoming drug resistance and are currently accruing to this clinical trial in a phase I setting. We have also studied other small molecules such as cyclin dependent kinase inhibitors and neutralizing antibodies to B-cell activating factor (BAFF). These compounds are being tested in phase I/II clinical studies based on strong preclinical rational and efficacy in our myeloma model systems. All of these clinical trials are backed by translational research endpoints informed by our preclinical studies with the view to validating our data.
Bone Biology and Therapeutics
Bone disease affects a broad range of conditions including postmenopausal osteoporosis; Pagets disease; bone metastasis in breast, lung, and prostate cancers; and primary tumor cell involvement in Multiple Myeloma (MM). Normal bone physiology is a dynamic process involving a balance between bone formation and resorption. In disease states like MM, the balance is tilted towards excessive bone resorption because of increased osteoclastic activity, resulting in osteolytic bone disease. In contrast, osteoblasts are markedly suppressed and very little if any osteoblastic activity is noted. An understanding of bone remodelling in normal physiology and in the context of disease is a focus of interest with emphasis on targeting this balance with novel therapeutics. Our studies have included several small molecule inhibitors and antibody based strategies with the view to restore normal balance in bone remodelling.
Noopur Raje, MD