Advances in Pancreatic Ductal Adenocarcinoma Treatment

Simple Summary:& nbsp;Pancreatic cancer remains one of the most challenging malignancies to treat with standard approaches. Emerging treatment approaches incorporating innovative surgical techniques and novel systemic therapies may help to improve outcomes for pancreas cancer patients. Although immunotherapy has proven to be less effective for the treatment of pancreas cancer relative to more immunogenic tumor types, multiple immune system stimulating agents are under active investigation for pancreatic ductal adenocarcinoma, either alone or in combination with other therapeutic agents. The tumor microenvironment of pancreatic cancer is also an attractive therapeutic target given that it is believed to be highly immunosuppressive and encapsulated by a dense stroma. This review article aims to summarize pre-clinical and clinical studies, including ongoing clinical trials, which attempt to incorporate novel treatment approaches for pancreas cancer. Emerging treatment approaches may help to significantly improve outcomes for this tough to treat disease. Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest malignancies among all cancers. Despite curative intent, surgery and the use of standard cytotoxic chemotherapy and radiation therapy, PDAC remains treatment-resistant. In recent years, more contemporary treatment modalities such as immunotherapy via checkpoint inhibition have shown some promise in many other malignancies, yet PDAC still eludes an effective curative treatment. In investigating these phenomena, research has suggested that the significant desmoplastic and adaptive tumor microenvironment (TME) of PDAC promote the proliferation of immunosuppressive cells and act as major obstacles to treatment efficacy. In this review, we explore challenges associated with the treatment of PDAC, including its unique immunosuppressive TME. This review examines the role of surgery in PDAC, recent advances in surgical approaches and surgical optimization. We further focus on advances in immunotherapeutic approaches, including checkpoint inhibition, CD40 agonists, and discuss promising immune-based future strategies, such as therapeutic neoantigen cancer vaccines as means of overcoming the resistance mechanisms which underly the dense stroma and immune milieu of PDAC. We also explore unique signaling, TME and stromal targeting via novel small molecule inhibitors, which target KRAS, FAK, CCR2/CCR5, CXCR4, PARP and cancer-associated fibroblasts. This review also explores the most promising strategy for advancement in treatment of pancreatic cancer by reviewing contemporary combinatorial approaches in efforts to overcome the treatment refractory nature of PDAC.

Automated summary

Pancreatic cancer, with its highly immunosuppressive tumor microenvironment and dense stroma, presents challenges for traditional treatment approaches. Emerging treatment strategies have the potential to significantly improve outcomes for pancreatic cancer patients.