Computational analysis of 5-fluorouracil anti-tumor activity in colon cancer using a mechanistic pharmacokinetic/pharmacodynamic model

Computational modeling plays an essential role in predicting the outcome of chemotherapy and developing optimal dosing strategies. In this study, we developed a computational model examining the influence of a chemotherapeutic agent, 5-fluorouracil, on tumor proliferation. 5-fluorouracil is a standard chemotherapeutic agent used to treat solid cancers such as breast, colon, head, and neck. Our model traces the dynamics of critical intermediate components and generates the accurate tumor response prediction in a physiologically-based manner for colon cancer. The comprehensive model simulates the tumor volume change under various dosage regimens, and its generalizability is attested by the validation against literature data. We used the models to investigate potential causes of the tumor resistance to 5-fluorouracil. Our model simulations for various dosage regimens help quantify the relationship between treatment protocols and chemotherapy potency