Date of Award

2018

Document Type

Open Access Thesis

Degree Name

MS in Physician Assistant Studies (PA)

Department

Physician Assistant Studies

First Advisor

Stephanie Elko

Abstract

5-fluorouracil (5-FU) is a pyrimidine analog that has been successfully employed in anticancer therapy for over forty years. Over the past several decades, researchers have characterized its cellular and clinical pharmacology and uncovered multiple mechanisms of action, which include the inhibition of thymidylate synthase (TS) and incorporation of its metabolites into DNA and RNA. The purpose of this quantitative systemic review was to summarize and evaluate what is known of these mechanisms to determine which are of most significance in the anticancer effects of 5-FU in metastatic colorectal cancer (mCRC) patients. A literature search of peer-reviewed articles dating back to the discovery of 5-FU did not find evidence to conclusively satisfy this inquiry, mainly due to a lack of relevant research in human models and uncertainty regarding the impact of DNA and RNA repair processes in tumor cells following drug administration. Overall, the literature did not support the current assumption that DNA-based mechanisms are definitively most responsible for the efficacy of 5-FU, and underscores the importance of better understanding how 5-FU promotes cell death and how tumors develop resistance to it. Future research could be directed toward further elucidating the mechanistic details of 5-FU treatment in humans, as well as discovering clinically useful biomarkers to better optimize and personalize metastatic colorectal cancer therapies.

Identifier

SC11.PAS.2018.Smits.N

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