Unravelling the pathogenesis and therapeutic approaches of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the aggressive cancers having high metastasis, late progression and resistance to therapies. PDAC arises from the ductal epithelium of the pancreas. The tumour microenvironment plays a key role in metastasis. One of the reasons behind PDAC being so aggressive as a cancer is that it forms a dense stroma around the neoplastic epithelium, which contributes to further tumour progression, invasion, metastasis and drug resistance. The key components of PDAC include the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs) and vasculature. The dense stroma in the ECM prevents drug penetration into cancer cells, making PDAC more challenging to treat. The oncogenic KRAS mutation is mainly responsible for the initiation, progression, immune evasion and further therapy resistance in this cancer. Despite having a low rate of survival, therapies available for this cancer are now emerging and developing rapidly. There are many more therapies now available for the treatment of PDAC, including immunotherapies, targeted gene therapies, stroma-targeting therapies and novel chemotherapies, which are much more promising in this cancer. This article focuses on the pathogenesis of PDAC and the various recent therapies used to treat it. It further discusses future perspectives in the treatment of this cancer, AI-driven therapies and challenges in this field.