Senior Scientist Merck & Co Inc West Point, Pennsylvania
Tumor cells have been found to express a host of drug metabolizing enzymes. The expression of P450 enzymes in tumor tissue may play a role in decreasing drug concentrations within tumor, ultimately decreasing the effectiveness of chemotherapeutic drugs. In this study we utilized CT26 tumor cell line commonly used in oncology drug discovery. Our results showed that four of the seven P450 substrates exhibited metabolite formation in CT26 cells, confirming Cyp activity in the tumor cells. Proteomics analysis showed increased expression of Cyp20a1 and Cyp2c55 among other proteins in the CT26 tissue, relative to their levels in control tissue. PBPK models were used to evaluate the combined effects of tumor clearance and permeability on the resulting tumor concentrations of a given drug. Ultimately, the work demonstrates the importance of understanding the role of tumor metabolism on unbound drug concentrations which are able to then interact within their pharmacological targets.
Learning Objectives:
After completion, participants will have a better understanding of the role of tumor metabolism in drug concentration and its interaction with pharmacological targets.
