Department of Cancer Biology, Chair
Roswell Park Cancer Institute
Tel: 716-845-2389
Fax: 716-845-7609
youcef.rustum@roswellpark.org

Academic Research Professor, Molecular Pharmacology and Cancer Therapeutics Program
Roswell Park Graduate Division
Associate Vice Provost
University at Buffalo
Professor of Oncology
University of Xian in China
 

Dr. Youcef M. Rustum joined the staff of Roswell Park Cancer Institute (RPCI) in 1970. He is Chair of the Department of Cancer Biology and also serves as a Research Professor, Molecular Pharmacology and Cancer Therapeutics Program, Roswell Park Graduate Division, University at Buffalo; and served as Associate Dean, University at Buffalo School of Medicine & Biomedical Sciences; and Professor and Director of Urologic Research, Department of Urologic Oncology, University at Buffalo. He was named a Professor of Oncology for the University of Xian in China in 2008.

He most recently served as the Senior Vice President for Science Administration and as Director of the Institute Core Resources before returning to his research full-time. He earned his doctoral degree in Biochemical Pharmacology at the University at Buffalo (UB) in 1970.

His research interests focus on translational research based on knowledge gained from research focused on molecular control of cell cycle, apoptosis and metabolic modulation of drug sensitivity and resistance. The hope is to develop new and novel treatments for cancer patients, with emphasis on colorectal, head and neck, and breast cancers. For more details on his research program, please see below.

Dr. Rustum is a member of the American Society for Clinical Oncology, American Association for Cancer Research (AACR), American College of Clinical Pharmacology, American Physiological Society, American Society for Clinical Pharmacology and Therapeutics, International Association for Comparative Research on Leukemia and Related Diseases, and American Society for Pharmacology and Experimental Therapeutics. Currently, he serves on the Board of Advisors, Bayer Pharmaceuticals, Roche Pharmacueticals, BioNumerik Pharmaceuticals and the National Surgical Adjuvant Breast and Bowel Projects (NSABP), the Board of Directors of the Meta-Analysis Group in Cancer, Chair of the Board of King Hussein Cancer Center in Jordan and several committes at RPCI and UB.

Dr. Rustum has authored or co-authored more than 300 peer-reviewed publications, and book chapters. He serves on the Editorial Board of the Journal of Clinical Oncology, Clinical Colorectal Cancer, Anticancer Drugs, Investigational New Drugs (IND), Clinical Cancer Research.

Research Program: Molecular Therapeutic Drug Selectivity and Drug Resistance

The focus of this laboratory is to identify mechanisms predictive for therapeutic outcome to a selected agent representing Topoisomerase I poison and antimetabolites as examples of agents studied in this laboratory.

The ultimate goal is to translate knowledge gained in the laboratory into the design of clinical trials with the hope of altering drug efficacy and enhancing quality of life. The staff in this laboratory are focused on translational research (bench to bedside and vice versa) with a particular emphasis on the development of new drugs with greater therapeutic efficacy and selectivity and validation of the therapeutic effect in the clinical setting.

Cellular responses are determined initially in in vitro assays, including those which determine responses of individual cells, and results are analyzed using new quantitative approaches to reveal the nature and intensity of drug interactions. Studies are conducted at the molecular level through determination and manipulation of gene expression. Of particular interest are those proteins involved in cell cycle control and apoptosis. Ideas generated by these studies are then tested in vivo in unique animal models, and brought to clinical trial for validation.

Overview of Major Achievements

• Lead the effort in the preclinical development and clinical validation of Roswell Park Cancer Institute, 5-fluorouracil/leucovorin schedule, a standard regimen for patients with advanced colorectal cancer.
• Demonstrated that selenium containing compounds are highly effective modulators of the therapeutic efficacy (cures) and selectivity of anticancer drugs.
• Based on preclinical results, selenium is now being evaluated in phase I/II clinical trial.
• Mechanistically, selenium is an effective modulator of caspase-dependent and independent apoptosis as well as inhibitor of angiogenesis through inhibition of HIF-1a and VEGF expression.
• Cyclin E-Cdk2 activation is coupled to cell cycle arrest and inhibition of DNA replication induced by the thymidylate synthase inhibitor, raltitrexed.
• Overexpression of Bax laters the mechanism of drug-induced cell death in human head and neck carcinoma A253 tumor cells. Cyclin D1-Cdk5 overexpression and MCM3 cleavage are involved in bax-associated spontaneous apoptosis and differentiation in a human head and neck carcinoma xenograft model (A253).
• Development of a new semiparametric approach for the assessment of the combined-action of anticancer agents, and development of a new pharmacodynamic paradigm for modeling in vitro drug cytotoxicity and in vivo resistance.

Key Publications

• Hapke G, Yin MB, Wu J, Frank C, Rustum YM. Phosphorylation of chk1 at serine-345 affected by topoisomerase I poison SN-38. Int J Oncol. 21(5):1059-1066, 2002.
• Naka T, Sugamura K, Hylander BL, Widmer MB, Rustum YM, Repasky EA. Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutics agents on patients' colon tumors rown in SCID mice. Cancer Res. 62(20):5800-5806, 2002.
• Wu J, Yin MB, Hapke G, Toth K, Rustum YM. Induction of biphasic DNA double strand breaks and activation of multiple repair protein complexes by DNA topoisomerase I drug 7-ethyl-10-hydroxy-camptothecin. Mol Pharmacol. 61(4):742-748, 2002.
• Yin MB, Hapke G, Wu J, Azrak RG, Frank C, Wrzosek C, Rustum YM. Chk 1 signaling pathways that mediated G(2)M checkpoint in relation to the cellular resistance to the novel topooisomerase I poison BNP1350. Biochem Biophys Res Commun. 295(2):435-444, 2002.
• Faessel HM, Slocum HK, Rustum YM, Greco WR. Thymidine and hypoxanthine protection patterns of the folic acid-enhanced synergies for synthesis against human ileocecal HCT-8 cells. Int J Oncol. 23(2):401-409, 2003.
• Tewes M, Schleucher N, Achterrath W, Wilke HJ, Frings S, Seeber S, Harstrick A, Rustum YM, Vanhoefer U. Capecitabine and irinotecan as first-line chemotherapy in patients with metastatic colorectal cancer: results of an extended phase I study dagger. Ann Oncol. 14(9):1442-1448, 2003.
• Azrak RG, Cao S, Slocum HK, Toth K, Durrani FA, Yin M-B, Pendyala L, Zhang W, McLeod HL, and Rustum YM. Therapeutic synergy between irinotecan and 5-fluorouracil against human tumor xenografts. Clin Cancer Res., 10:1121-1129, 2004.
• Cao S, Durrani FA, and Rustum YM. Selective modulation of the therapeutic efficacy of anticancer drugs by selenium containing compounds against human tumor xenografts. Clin Cancer Res., 10:2561-2569, 2004.
• Yin M-B, Li Z-R, Cao S, Durrani FA, Azrak RG, Frank C, and Rustum Y.M. Enhanced 7-Ethyl-10-hydroxycamptothecin (SN-38) Lethality by Methylselenocysteine is Associated with Chk2 Phosphorylation at Threonine-68 and Down-Regulation of Cdc6 Expression. Molecular Pharmacology, 1:153-160, 2004.