FIGURE 4.

Oxidative stress induces damage response, and the selection of surviving clones presents new therapeutic targets against pancreatic ductal adenocarcinoma (PDAC). A, Oxidative stress induces damage responses in pancreatic cells, which can elicit the repair of deleterious alterations. The schema indicates that the resultant surviving cells harbor mutations or abnormalities, such as KRAS, P16INK4A, TP53, and SMAD4 and telomere shortening, whereas cell death was induced in heavily damaged cells, which induce immune response. ²⁰ B, The surviving cells may expand, and dead cells will be eliminated from PDAC tissues, which will give rise to clonal evolution, as demonstrated by clinical sequencing analysis ⁴⁴ , ⁴⁵