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Published on: January 17, 2025
Management of Advanced Pancreatic Cancer through Stromal Depletion and Immune Modulation
Tiantong Liu1, Sihang Cheng2, Qiang Xu1
1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100006, China.
Abstract:
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Unfortunately, therapeutic gains in the treatment of other cancers have not successfully translated to pancreatic cancer treatments. Management of pancreatic cancer is difficult due to the lack of effective therapies and the rapid development of drug resistance. The cytotoxic agent gemcitabine has historically been the first-line treatment, but combinations of other immunomodulating and stroma-depleting drugs are currently undergoing clinical testing. Moreover, the treatment of pancreatic cancer is complicated by its heterogeneity: analysis of genomic alterations and expression patterns has led to the definition of multiple subtypes, but their usefulness in the clinical setting is limited by inter-tumoral and inter-personal variability. In addition, various cell types in the tumor microenvironment exert immunosuppressive effects that worsen prognosis. In this review, we discuss current perceptions of molecular features and the tumor microenvironment in pancreatic cancer, and we summarize emerging drug options that can complement traditional chemotherapies.
Insights
Pancreatic cancer treatment faces challenges due to drug resistance and tumor heterogeneity. Emerging therapies targeting molecular features and the tumor microenvironment offer new hope alongside traditional chemotherapy.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Pancreatic cancer remains a leading cause of cancer mortality globally.
- Current treatments, including gemcitabine, show limited efficacy and face rapid drug resistance.
- Tumor heterogeneity and immunosuppressive microenvironments complicate management strategies.
Purpose of the Study:
- To review current understanding of pancreatic cancer's molecular features and tumor microenvironment.
- To summarize novel therapeutic strategies for pancreatic cancer.
- To explore emerging drug options complementing conventional chemotherapies.
Main Methods:
- Literature review of current research on pancreatic cancer.
- Analysis of molecular alterations and expression patterns.
- Summary of ongoing clinical trials for new therapeutic combinations.
Main Results:
- Pancreatic cancer exhibits significant heterogeneity, limiting the clinical utility of defined subtypes.
- Tumor microenvironment components contribute to immune suppression and poor prognosis.
- Several novel therapeutic agents targeting molecular pathways and the stroma are in clinical development.
Conclusions:
- Understanding molecular features and the tumor microenvironment is crucial for advancing pancreatic cancer treatment.
- Emerging therapies show promise in overcoming resistance and improving outcomes.
- Combination strategies integrating novel drugs with chemotherapy are essential for future management.
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