Journal Article

Regulation of thymidylate synthase: an approach to overcome 5-FU resistance in colorectal cancer

Thareja, Suresh, Singh, Ankit Kumar, Kumar, Pradeep, Kumar, Adarsh, Singh, Harshwardhan

2022

Overview

Thymidylate synthase is the rate-limiting enzyme required for DNA synthesis and overexpression of this enzyme causes resistance to cancer cells. Long treatments with 5-FU cause resistance to Thymidylate synthase targeting drugs. We have also compiled different mechanisms of drug resistance including autophagy and apoptosis, drug detoxification and ABC transporters, drug efflux, signaling pathways (AKT/PI3K, RAS-MAPK, WNT/β catenin, mTOR, NFKB, and Notch1 and FOXM1) and different genes associated with resistance in colorectal cancer. We can overcome 5-FU resistance in cancer cells by regulating thymidylate synthase by natural products ( Coptidis rhizoma) , HDAC inhibitors, mTOR inhibitors, Folate antagonists, and several other drugs which have been used in combination with TS inhibitors. This review is a compilation of different approaches reported for the regulation of thymidylate synthase to overcome resistance in colorectal cancer cells. Graphical abstract

• Publisher: Springer US,Springer Nature B.V
• Subject: Apoptosis / Autophagy / Cancer therapies / Cell cycle / Chemotherapy / Colonoscopy / Colorectal cancer / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - genetics / Colorectal Neoplasms - metabolism / Dihydrofolate reductase / Drug resistance / Drug Resistance, Neoplasm / Enzymes / Fluorouracil - pharmacology / Fluorouracil - therapeutic use / Hematology / Humans / Inflammation / Internal Medicine / Kinases / Large intestine / Life expectancy / Lymphatic system / Medicine / Medicine & Public Health / Mutation / Oncology / Pathology / Proteins / Radiation / Rectum / Review Article / Signal Transduction / Surgery / Thymidylate Synthase - genetics / Thymidylate Synthase - metabolism