TP53 and colorectal neoplasm: Further studies would need to evaluate the interplay between combined use of 5-FU and irinotecan as compared to 5-FU alone with regard to p53-dependent regulation of DPYD. The idea that mutant p53 could through derepression up-regulate DPYD as a resistance mechanism to 5-FU treatment is also a focus of future research as 5-FU is used in multiple consecutive regimens in the therapy of evolving colorectal tumors.