Steven T. Rosen, MD Genevieve Teuton Professor of Medicine Director, Robert H. Lurie Comprehensive Cancer Center Biologic therapies of cancer Curricula: Cancer Biology Pharmacology and Toxicology E-mail:   s-rosen@northwestern.edu

Our laboratory focuses on understanding the molecular pathways underlying biologic therapies of cancer and in specific the hormonal and nucleoside analog treatment of hematologic malignancies. Glucocorticoids are the standard of treatment for a variety of hematologic malignancies with very little understanding of the pathways involved. We have identified glucocorticoid-regulated genes in an effort to elucidate those pathways and discover additional cellular targets. Information from these studies will be applied to understanding the glucocorticoid resistant tumor states.

A second major interest in the laboratory is to develop therapeutic approaches that are effective in glucocorticoid resistant tumors. We have identified two nucleoside analogs that induce programmed cell death in hematologic malignancies. We are further investigating the mechanism by which these compounds cause cytotoxicity in myeloma cell lines including examination of the pathways of apoptosis, the consequences of the incorporation of these nucleoside analogs into DNA and RNA and their effect on the phosphorylation of key signaling pathways in the cell. We are currently doing pre-clinical testing of these drugs to determine efficacy for the treatment of multiple myeloma with the goal of moving these drugs into the clinical arena.

Publications:

Gandhi V, Ayers M, Halgren RG, Krett NL, Newman RA, and Rosen ST. 8-Chloro-cAMP and 8-Chloro-Adenosine Act by Same Mechanism in Multiple Myeloma Cells. Cancer Research 61: 5474-5479, 2001.

Greenstein S, Ghias K, Krett NL, and Rosen ST. Mechanisms of Glucocorticoid-mediated Apoptosis in Hematological Malignancies. Clinical Cancer Research 8: 1681-1694, 2002.

Nabhan C, Gajria D, Krett NL, Gandhi V, Ghias K, and Rosen ST. Caspase activation is required for gemcitabine activity in multiple myeloma cell lines. Molecular Cancer Therapeutics 1: 1221-1227, 2002.

Greenstein S, Krett NL, Kurosawa Y, Ma C, Chauhan D, Hideshima T, Anderson KC, and Rosen ST. Characterization of the MM.1 human multiple myeloma (MM) cell lines: A model system to elucidate the characteristics, behavior and signaling of steroid-sensitive and resistant MM cells. Experimental Hematology 31:271-282, 2003.