Pancreatic ductal adenocarcinoma (PDAC) represents the most common malignant tumor of the pancreas. Researchers have discovered genetic aberrations that occur during PDAC development and progression.

The search was performed among recently published articles in English on PubMed database and findings presented at recent meetings using keywords of Pancreatic ductal adenocarcinoma; Oncogenic KRAS; KRAS inhibitors; Treatment.

In most cases, the oncogenic mutant KRAS makes PDAC, which has been able to drive pancreatic neoplasia. In reality, nearly 95% of the PDAC harbor mutationally activated KRAS, but to date there are no effective treatments that target this mutant protein. The oncogenic KRAS plays a main role in controlling tumor metabolism by orchestrating multiple metabolic changes including stimulation of glucose uptake, differential channeling of glucose intermediates, increased autophagy, and macropinocytosis. However, all attempts to target KRAS have been directly failed and KRAS has been widely considered to be incurable. This has led to intense efforts to identify drug able critical downstream targets and nodes orchestrated by mutationally activated KRAS. In this review, we will discuss about the latest advances in oncogenic KRAS signalling and discuss how these could benefit PDAC treatment in the future.

Contrary to these findings, the full dependence of PDAC tumors on endogenous KRAS remains unknown, which is a requisite for the favorable clinical development of novel KRAS inhibitors.