Figure 1. Genetic mutations in PDAC initiation and development.
(A) Multi-stage initiation and progression model of PDAC. As cells acquire mutations in genes like KRAS, CDKN2A, TP53 and SMAD4, along with other less commonly mutated genes, the lesion progresses from low grade pancreatic intraepithelial neoplasia (PanIN1) through PanIN2 and high grade PanIN3, and ultimately to become invasive adenocarcinoma. In PDAC, intrinsic signals such as the KRASG12D mutation and extrinsic signals like EGFR activation contribute to an immune-suppressive and desmoplastic microenvironment through reciprocal interactions between tumor cells and diverse stroma cells. Examples of these stroma cells include cancer-associated fibroblasts (blue), cancer-associated macrophages (pink), myeloid-derived suppressor cells (green), among others. (B) Prevalence of KRAS mutant variants in human pancreatic cancer.