Irinotecan and vandetanib create synergies for treatment of pancreatic cancer patients with concomitant TP53 and KRAS mutations

Background: The most frequently mutated gene pairs in pancreatic adenocarcinoma (PAAD) are KRAS and TP53, and our goal is to illustrate the multiomics and molecular dynamics landscapes of KRAS/TP53 mutation and also to obtain prospective novel drugs for KRAS- and TP53-mutated PAAD patients. Moreover, we also made an attempt to discover the probable link amid KRAS and TP53 on the basis of the abovementioned multiomics data. Method: We utilized TCGA Cancer Cell Line Encyclopedia data for the analysis of KRAS/TP53 mutation in a multiomics manner. In addition to that, we performed molecular dynamics analysis of KRAS and TP53 to produce mechanistic descriptions of particular mutations and carcinogenesis. Result: We discover that there is a significant difference in the genomics, transcriptomics, methylomics, and molecular dynamics pattern of KRAS and TP53 mutation from the matching wild type in PAAD, and the prognosis of pancreatic cancer is directly linked with a particular mutation of KRAS and protein stability. Screened drugs are potentially effective in PAAD patients. Conclusions: KRAS and TP53 prognosis of PAAD is directly associated with a specific mutation of KRAS. Irinotecan and vandetanib are prospective drugs for PAAD patients with KRAS(G12D) mutation and TP53 mutation.

Automated summary

The study revealed significant differences in the genomics, transcriptomics, methylomics, and molecular dynamics between KRAS and TP53 mutations from the wild type in PAAD, with the prognosis of pancreatic cancer directly linked to specific KRAS mutations and protein stability. Screened drugs show potential effectiveness for PAAD patients.