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Deciphering the Resistance Profile of Cancerous Thymidylate Synthase

Thymidylate Synthase (TSase) is an enzyme that converts 2′‐deoxyuridinemonophosphate (dUMP) to thymidylate (dTMP), a base for DNA. Since there is no other de novo route to dTMP in cells, TSase is critical to cell replication and survival. 5F‐dUMP – produced intracellularly from the chemotherapeutic pro‐drug 5‐fluorouracil (5‐FU) – inhibits TSase, thus halting the supply of the DNA base thymidylate, causing cessation of DNA synthesis and leading to thymine‐less cell death. While it is very common for pathogenic organisms to become resistant to certain antibiotic drugs, cancerous cells have also developed some mechanisms to cope with the cytotoxic effect of chemotherapeutic drugs. 1