Biochemistry & Molecular Biology
Keck School of Medicine
USC / Norris Comprehensive Cancer Center
Cancer Cell Biology
DNA & RNA
The work in this laboratory is directed at understanding the mechanisms by which cytotoxic anti-cancer drugs interact with their intracellular targets and the molecular factors and events determining response of tumors to drugs. Innate drug sensitivity of tumors as well as acquired resistance may be due to quantitative and qualitative changes in the expression of genes of target enzymes and activating enzymes. We have developed methods for quantitating gene expression by PCR and for rapid mutation detection by RNA conformational analysis. The latter technique is being used to investigate the role of mutations in acquired drug resistance. By using quantitative PCR, we have shown substantial variation among tumors in the degree of expression of genes of drug-targeted enzymes such as thymidylate synthase. Studies are under way to identify factors that alter the normal expression of these genes in cancer cells.