Research focus is the improvement of cancer chemotherapy by understanding the factors that contribute to interindividual variability in drug response. Dr. Blanco‘s goal is to perform translational research using a combination of approaches based on a) the analysis of biological samples from selected populations, and b) the use of informative laboratory models.

A project in Dr. Blanco‘s laboratory is related to the understanding of the factors that govern interindividual variability in the metabolism and disposition of the anthracyclines doxorubicin and daunorubicin. It is possible that specific sequence variations in genes associated with the metabolism and disposition of anthracyclines may impact the risk of cardiotoxicity in some individuals. Our efforts are focused on the discovery and characterization of novel single-nucleotide polymorphisms in a family of genes involved in the metabolism of anthracyclines in liver, heart and different types of tumors (e.g. breast and lung cancer). We are investigating the extent of DNA sequence variation in these selected gene candidates among normal individuals from different ethnic groups. We will study genotype-phenotype correlations by using paired tissue-DNA-RNA samples available from my collaborators from the Pharmacogenetics of Anticancer Agents Research group (PAAR,http://www.pharmacogenetics.org/), and from the Roswell Park Cancer Institute (RPCI, http://www.roswellpark.org/document_9.html). We will expand our studies to characterize the functional effect of the genetic variants by using different in-vitro and in-vivo models (e.g. cultures of hepatocytes, cardiomyocytes, transgenic mice).

Our findings are being translated into informative case-control epidemiological studies. I am a co-investigator in the project entitled "Cardiac events among survivors of childhood and adolescent cancer - Role of gene-environment interactions" (PI: Smita Bhatia, City of Hope National Medical Center, CA). The project is sponsored by the Childhood Cancer Survivor Study Group (The Children‘s Oncology Group http://www.childrensoncologygroup.org/), and supported by a grant from the Lance Armstrong Foundation. We are analyzing the distribution of the candidate polymorphisms in identically treated patients who have vs. have not developed congestive heart failure (CHF) after anthracycline treatment for childhood cancer. In the future, individualizing the dosing of anthracyclines based on genetic characteristics might minimize the occurrence of adverse effects.