DPYD and neoplasm: Many factors can contribute to the progression of 5-FU resistance, such as TYMS overexpression, resistance to apoptosis, enhanced autophagy, EMT pathway, increased efflux of drugs mediated by the family of transporter proteins, increased activity of the dihydropyrimidine dehydrogenase (DPD), the generation of DNA mismatch repair defects, and the hypoxic microenvironment in tumor tissues[13,36].