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Current and Emerging Therapies in Metastatic Pancreatic Cancer
Gulam Abbas Manji1, Kenneth P Olive2, Yvonne M Saenger3
1Division of Medical Oncology, Columbia University Medical Center, and New York Presbyterian Hospital, Herbert Irving Pavilion, New York, New York. gam2140@cumc.columbia.edu.
Abstract:
Targeted therapies and immunotherapy have changed the face of multiple solid malignancies, including metastatic melanoma and lung cancer, but no such therapies exist for pancreatic ductal adenocarcinoma (PDAC) despite the knowledge of key mutations and an increasing understanding of the tumor microenvironment. Until now, most clinical studies have not been biomarker driven in this highly immunosuppressive and heterogeneous cancer. Ongoing basic and translational studies are better classifying the disease in hopes of identifying critical pathways that distinguish the unique PDAC subtypes, which will lead to personalized therapies. In this review, we discuss the current treatment options for metastatic pancreatic cancer and highlight current ongoing clinical trials, which aim to target the stroma and the immune microenvironment either alone or in combination with standard chemotherapy. Identifying biomarkers and key resistance pathways and targeting these pathways in a personalized manner in combination with chemotherapy are likely to yield a more immediate and durable clinical benefit. Clin Cancer Res; 23(7); 1670-8. ©2017 AACRSee all articles in this
Insights
Despite advances in other cancers, effective targeted therapies for pancreatic ductal adenocarcinoma (PDAC) are lacking. Research is focusing on personalized treatments by targeting the tumor microenvironment and identifying biomarkers for better outcomes.
Area of Science:
- Oncology
- Cancer Research
Background:
- Metastatic melanoma and lung cancer have benefited from targeted therapies and immunotherapy.
- Pancreatic ductal adenocarcinoma (PDAC) currently lacks such targeted treatments despite known mutations and a developing understanding of its tumor microenvironment.
Purpose of the Study:
- To review current treatment options for metastatic pancreatic cancer.
- To highlight ongoing clinical trials targeting the stroma and immune microenvironment.
- To discuss the potential of personalized therapies based on biomarkers and resistance pathways.
Main Methods:
- Review of current treatment strategies for metastatic pancreatic cancer.
- Analysis of ongoing clinical trials focused on novel therapeutic targets.
- Discussion of basic and translational research classifying PDAC subtypes.
Main Results:
- Most clinical studies in PDAC have not been biomarker-driven.
- PDAC is characterized by an immunosuppressive and heterogeneous tumor microenvironment.
- Targeting the stroma and immune microenvironment, alone or with chemotherapy, is a focus of current trials.
Conclusions:
- Personalized therapies targeting specific PDAC subtypes are under development.
- Identifying biomarkers and resistance pathways is crucial for durable clinical benefit.
- Combination therapies involving chemotherapy and novel agents show promise for treating pancreatic cancer.