NSC-319726 is a preclinical mutant p53 activator recognized as a critical process in the pancreatic tumor development . The clinical development of p53 activators, particularly MDM2 antagonists, and their relevance in pancreatic tumor development have been earlier reported . Notably, idasnutlin, an MDM2 antagonist, has entered phase III testing, signifying its advancement in clinical evaluation . Likewise, AZD-8055 is an mTOR (mechanistic target of rapamycin) inhibitor that has been investigated for its potential therapeutic value in various cancer types, including pancreatic tumors . The therapeutic exploitation of autophagy's role in pancreatic cancer has been explored through clinical trials using autophagy inhibitors, specifically chloroquine and hydroxychloroquine. However, these inhibitors have not shown significant clinical benefits in the metastatic stage of pancreatic cancer . The lack of clinical benefits from autophagy inhibition may be due to the fact that clinically safe doses of drugs do not inhibit autophagy enough to have a significant effect . In pancreatic cancer, where KRAS is activated and p53 is disabled, cells can tolerate low levels of autophagy because the KRAS/BRAF/MAPK cascade sends inhibitory signals and p53 transcription is disabled, reducing autophagy protein levels. To achieve a clinically significant decrease in autophagy levels, inhibition of the KRAS/BRAF/MAPK cascade may be necessary, as this could have a synergistic effect with autophagy inhibition . The loss of p14ARF in pancreatic cancer cells may reduce their ability to induce autophagy, which could potentially make these cancer cells more sensitive to autophagy inhibition . Inhibition of autophagy in cancer cells is being explored as a therapeutic strategy, as it can disrupt their survival mechanisms and enhance the efficacy of other treatments .