Robert B. Diasio, M.D.
Robert B. Diasio, M.D.
Robert Diasio, M.D. is a Professor of Pharmacology, Mayo Clinic College of Medicine and is the Director for the Mayo Clinic Cancer Center.
Dr. Diasio's research interests continue to focus on pharmacogenetics / pharmacogenomics as applied to cancer therapeutic agents. The effect of alterations in the expression of genes critical in drug uptake, activation, and catabolism can have a major impact on both toxicity (which typically have a narrow therapeutic index) as well as efficacy, potentially explaining why some patients respond to these drugs while others do not. Over the past two decades, his primary orientation has been of fluoropyrimidine drugs including 5-FU as well as the various oral fluoropyrimidines. The major tumors of interest have been colorectal cancer and other gastrointestinal tumors. Dr. Diasio's lab is now beginning to expand into other cancer therapeutic agents and other neoplasms. Specific current projects include: 1) Dihydropyrimidine Dehydrogenase (DPD) Deficiency as a Cause of Severe 5-FU Toxicity: a) Molecular studies clarifying causation - Role of transcription factors in DPD expression - Role of methylation of CpG islands in DPYD promoter - Role of regulatory regions in Intron 1 - Role of increased degradation proteosome, b) Developing a clinically useful diagnostic study - Combined phenotype-genotype population studies - Further clinical development of Uracil Breath Test, c) Examination of the causes for severe fluoropyrimidine toxicity not due to DPD deficiency - Dihydropyrimidinase deficiency - Beta-ureidpropionase deficiency - Role of genes controlling fluoropyrimidine anabolism. 2) Predictive value of expression of genes in tumor predicting tumor response: a) Colorectal Cancer - ECOG 5204 - correlative study evaluating role of predictive gene markers for 5-FU and Oxaliplatin, b) NSCLC - Role of EGFR mutations in predicting efficacy in NSC lung cancer. 3) Preclinical and Clinical Evaluation of DPD Inhibitory fluoropyrimidine (DIF) drugs: a) Optimizing the use of DPD inhibitors - Eniluracil, b) Use of prodrugs - Capecitabine - S-1
Clinical Pharmacology Section, Medicine Branch
Medical Oncology, Clinical Associate
Medicine (PGY 1 and 2)
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