Our goals are to understand mechanisms of drug resistance in cancer cells and to develop more effective therapies. Current research ranges from biochemical and molecular studies in cellular models to Phase I, II and III clinical trials of new inhibitors of drug resistance and novel therapies such as multi-targeted tyrosine kinase inhibitors and activators of TRAIL signaling.

Laboratory projects include studies of the multidrug transporter P-glycoprotein, regulation of the MDR1 gene, the role of beta tubulin gene expression in resistance to taxanes and vinca alkaloids, and the use of gene expression profiling in discovering molecular and genetic determinants of outcomes in cancer treatment.

Clinical investigations include the prognostic significance of resistance gene expression in cancers, pharmacokinetic consequences of MDR modulation, development of new modulators of drug resistance, and clinical trials of a monoclonal antibody agonist of TRAiL-R2 receptor, as well as a small molecule inhibitor of multiple tyrosine kinase signaling proteins. We have developed and are completing Phase II trials of the IFOX regimen (gefitininib, fluorouracil, leucovorin, oxaliplatin) in advanced colorectal cancer. We are performing pharmacogenetic and pharmacogenomic studies to investigate determinants of response and toxicities in these patients.

• Central European Oncology Congress, Opatija, Croatia More 

• Chan JK, Ueda SM, Sugiyama VE, Stave CD, Shin JY, Monk BJ, Sikic BI, Osann K, Kapp DS "Analysis of Phase II Studies on Targeted Agents and Subsequent Phase III Trials: What Are the Predictors for Success?" J Clin Oncol 2008; More
• Juric D, Lacayo NJ, Ramsey MC, Racevskis J, Wiernik PH, Rowe JM, Goldstone AH, O'dwyer PJ, Paietta E, Sikic BI "Differential Gene Expression Patterns and Interaction Networks in BCR-ABL-Positive and -Negative Adult Acute Lymphoblastic Leukemias." J Clin Oncol 2007; More
• Juric D, Bredel C, Sikic BI, Bredel M "Integrated high-resolution genome-wide analysis of gene dosage and gene expression in human brain tumors." Methods Mol Biol 2007; 377: 187-202 More
• Bredel M, Bredel C, Juric D, Duran GE, Yu RX, Harsh GR, Vogel H, Recht LD, Scheck AC, Sikic BI "Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas." J Clin Oncol 2006; 24: 2: 274-87 More
• Cho CD, Fisher GA, Halsey J, Sikic BI "Phase I study of gefitinib, oxaliplatin, 5-fluorouracil, and leucovorin (IFOX) in patients with advanced solid malignancies." Invest New Drugs 2006; 24: 2: 117-23 More