Pharmaceutica Analytica Acta

Pharmacogenomics predictions for breast cancer treatments? effi cacy and toxicity

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

Hugo A. Barrera-Salda?a

Scientific Tracks Abstracts: PAA

Abstract:

Breast cancer is the major cause of death among Mexican women between 35 and 50 years of age. Among the most prescribed chemotherapeutic agents are Capecitabine, a precursor of 5-fl ourouracil, which inhibits the synthesis of thymidine and DNA replication, and tamoxifen, a chemotherapeutic adjuvant that prevents recurrence in estrogen receptor positive patients that have undergone surgery. Capecitebine needs to be effi ciently eliminated by dihydropyrimidine dehydrogenase (DPD) to avoid its accumulation and adverse eff ects. Tamoxifen is a prodrug that needs the P450 liver enzyme isoform CYP2D6 for conversion to its active form, endoxifen. Th erefore, prediction of effi cacy and toxicity in breast cancer chemotherapy depends on pharmacogenomics. PHARMAchip ? is a DNAchip developed by Progenika Biopharma, SA (Bilbao, Spain) that consists of a microscopic slide carrying hundreds of oligonucleotides to screen for mutations and single nucleotide polymorphisms in genes of phase I, phase II, transporters, receptors and other enzymes and proteins with which drugs interact aft er entering the patient ́s body and metabolism. Among the genes present on this DNAchip genotype are those for the P450 and pyrimidine metabolism enzymes described above. We are using the PHARMAchip to investigate its usefulness as a predictor of chemotherapy effi cacy and toxicity in Mexican breast cancer patients. Th e fi rst fi ft y genomic DNAs from these patients analyzed reveal that most (almost 90%) patients carry a genotype corresponding to a phenotype of normal to extensive metabolism of tamoxifen with no mutations in the DPD gene that would otherwise cause 5-Fluorouracil derivative accumulation.

Biography :

he author completed his PhD at the age of 25 and is a distinguished alumnus from the University of Texas at Houston. His postdoctorate was at Louis Pasteur University in Strasbourg, France. He has created prestigious Molecular Biology Research and Graduate Programs and Centers in Mexico. He is the founder of Vitaxentrum, a premier Biotechnology and Genomics Consulting and Servicing Organization. He has published over 100 papers in prestigious journals and has served as reviewer of international journals and national academic committees. His team is recognized in Latin America as a pioneer and leader in molecular biology, DNA diagnostics, biotechnology, and gene therapy.