Landmark Series: Immunotherapy and Targeted Therapy for Pancreatic Cancer

Pancreatic cancer is one of the most aggressive gastrointestinal malignancies despite multimodality therapy. In the last several years, genomic studies have revealed that carcinogenesis is driven largely by key driver mutations that can be targeted for oncologic therapy. In addition, advances in cancer immunology have identified receptors and monoclonal antibodies that can be manipulated into harnessing the power of the host's immune system for antitumor treatment. These strategies have generated a paradigm shift in the management of several cancer types, including those in the gastrointestinal tract. However, there are several complicating factors when translating the results to pancreatic cancer, including the dense, fibrotic stroma unique to this disease that may shield the cancer cells from both cytotoxic and immunologic agents. Although the majority of trials have been performed in the metastatic setting, this review will focus on both the historic studies that have defined this field as well as the emerging data arising from ongoing efforts to exploit newly discovered mutations and their druggable targets.

Automated summary

Pancreatic cancer is an aggressive gastrointestinal malignancy, and recent genomic studies have identified key driver mutations that can be targeted for therapy. Advances in cancer immunology have also shown potential for utilizing the host's immune system for treatment. However, the unique fibrotic stroma of pancreatic cancer presents challenges in translating these strategies to clinical practice.