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Landmark Series: Immunotherapy and Targeted Therapy for Pancreatic Cancer
1Division of Surgical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. rochaf@ohsu.edu.
Abstract:
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.
Insights
Pancreatic cancer remains aggressive, but new genomic and immunology strategies offer targeted therapies. Overcoming the unique fibrotic stroma is key to effective treatment for this gastrointestinal malignancy.
Area of Science:
- Oncology
- Gastroenterology
- Immunology
Background:
- Pancreatic cancer is a highly aggressive gastrointestinal malignancy.
- Despite advances in multimodality therapy, outcomes remain poor.
- Genomic studies and cancer immunology have revealed new therapeutic targets.
Purpose of the Study:
- To review historic and emerging therapeutic strategies for pancreatic cancer.
- To discuss the challenges and opportunities in targeting pancreatic cancer.
- To highlight the potential of exploiting driver mutations and immune system manipulation.
Main Methods:
- Review of genomic studies identifying key driver mutations.
- Analysis of advances in cancer immunology and immunotherapeutic agents.
- Examination of challenges posed by the pancreatic tumor microenvironment, specifically the fibrotic stroma.
- Focus on both metastatic and emerging treatment settings.
Main Results:
- Genomic alterations provide targets for novel oncologic therapies.
- Immunologic approaches harness the host immune system for antitumor effects.
- The dense, fibrotic stroma of pancreatic cancer presents a significant barrier to treatment efficacy.
- Translational challenges exist in applying systemic therapies to pancreatic cancer.
Conclusions:
- Targeting driver mutations and leveraging immunotherapy represent a paradigm shift in cancer management.
- Overcoming the unique stromal characteristics of pancreatic cancer is crucial for therapeutic success.
- Ongoing research into newly discovered mutations and druggable targets holds promise for improved pancreatic cancer treatment.