Dr. Alan Lichtenstein and his colleagues are studying the molecular biology of multiple myeloma, chronic lymphocytic leukemia and squamous cell cancer of the head and neck. Their studies are directed at identifying molecules that are particularly abnormal in these diseases so that they can be targeted with novel forms of therapy. The research involves in vitro experimentation on tumor cells, studies of tumor growth in mice and clinical studies in patients with these diseases.
Lichtenstein and his colleagues investigate signal transduction pathways primarily in multiple myeloma cells. The researchers have been focusing on the AKT-mTOR pathway with the goal of developing anti-myeloma therapy with mTOR inhibitors. In this regard, current studies are evaluating how the level of AKT activity regulates the sensitivity of myeloma cells to mTOR inhibitors and how mTOR inhibitors can be used to induce apoptosis of myeloma cells in addition to the well known effects of cell cycle paralysis. Additional studies are examining the role of the microenvironment on myeloma cells with focus on fibronectin or bone marrow stromal cells as influences that protect myeloma cells from drug-induced apoptosis. Additional efforts are being made to identify abnormally mutated genes in head and neck cancers and chronic lymphocytic leukemia and, also, to specifically target the EB virus in patients with nasopharyngeal carcinoma.
Selected Cancer-Related Publications:
Luciano F, Krajewska M, Ortiz-Rubio P, Krajewski S, Zhai D, Faustin B, Bruey JM, Bailly-Maitre B, Lichtenstein A, Kolluri SK, Satterthwait AC, Zhang XK, Reed JC. Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma. Blood. 2007; 109(9): 3849-55.
Shi Y, Reiman T, Li W, Maxwell CA, Sen S, Pilarski L, Daniels TR, Penichet ML, Feldman R, Lichtenstein A. Targeting aurora kinases as therapy in multiple myeloma. Blood. 2007; 109(9): 3915-21.
Frost P, Shi Y, Hoang B, Lichtenstein A. AKT activity regulates the ability of mTOR inhibitors to prevent angiogenesis and VEGF expression in multiple myeloma cells. Oncogene. 2007; 26(16): 2255-62.
Yan H, Frost P, Shi Y, Hoang B, Sharma S, Fisher M, Gera J, Lichtenstein A. Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Cancer Res. 2006; 66(4): 2305-13.
Hoang B, Zhu L, Shi Y, Frost P, Yan H, Sharma S, Goodglick L, Dubinett S, Lichtenstein A. Oncogenic RAS mutations in myeloma cells selectively induce cox-2 expression, which participates in enhanced adhesion to fibronectin and chemoresistance. Blood. 2006; 107(11): 4484-90.