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Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future.
Literature Information
| DOI | 10.3322/caac.70035 |
|---|---|
| PMID | 40971231 |
| Journal | CA: a cancer journal for clinicians |
| Impact Factor | 232.4 |
| JCR Quartile | Q1 |
| Publication Year | 2025 |
| Times Cited | 0 |
| Keywords | early detection, folinic acid, 5‐fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), gemcitabine, pancreatic ductal adenocarcinoma (PDAC), screening |
| Literature Type | Journal Article, Review |
| ISSN | 0007-9235 |
| Authors | Alessandro Mannucci, Ajay Goel |
TL;DR
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer often diagnosed at advanced stages due to non-specific early symptoms and therapeutic resistance, with rising incidence linked to various risk factors. The study highlights advances in early detection methods, the importance of neoadjuvant chemotherapy for improving surgical outcomes, and the exploration of novel treatment strategies, including targeted therapies and combination approaches, which are crucial for enhancing patient survival and overcoming treatment challenges.
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early detection · folinic acid, 5‐fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) · gemcitabine · pancreatic ductal adenocarcinoma (PDAC) · screening
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis, largely because of late-stage diagnosis and therapeutic resistance. PDAC incidence has been rising, with modifiable and non-modifiable risk factors contributing to disease development. Chronic pancreatitis, diabetes mellitus, smoking, obesity, and familial predisposition have been implicated in PDAC pathogenesis. Early clinical manifestations are vague and insidious; therefore, PDAC is often diagnosed at an advanced stage, limiting curative treatment options. Efforts to improve early detection have focused on serum biomarkers (e.g., carbohydrate antigen 19-9), imaging modalities, and liquid biopsies. Endoscopic ultrasound and magnetic resonance imaging have demonstrated potential in identifying early-stage disease in certain high-risk populations. Surgical resection remains the only potentially curative option, but only 15%-20% of patients have resectable disease at diagnosis. Neoadjuvant chemotherapy has emerged as a promising strategy to improve resectability and survival outcomes. For patients with locally advanced or metastatic PDAC, combination chemotherapy regimens such as FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin), NALIRIFOX (5-fluorouracil, oxaliplatin, liposomal irinotecan, and leucovorin), and combined gemcitabine/nanoparticle albumen-bound paclitaxel offer survival benefits, although toxicity remains a concern, especially for platinum-based therapies. Several breakthroughs in molecular profiling have led to the development of targeted therapies, including sotorasib and olaparib. Immunotherapy has shown limited success in PDAC due to its immunosuppressive tumor microenvironment. However, novel combination approaches are under investigation, including quadruplet therapy, immune checkpoint inhibitors with oncolytic viruses, stromal-targeting agents, and personalized neoantigen vaccines. Key priorities for future research include identifying reliable biomarkers for early detection, refining patient selection for targeted therapies, and developing innovative strategies to overcome treatment resistance.
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Primary Questions Addressed
- What are the latest developments in serum biomarkers for the early detection of pancreatic cancer?
- How do modifiable risk factors for pancreatic cancer, such as obesity and smoking, influence prevention strategies?
- In what ways are novel combination therapies being tailored to address the unique challenges of pancreatic cancer treatment?
- What role does genetic profiling play in the selection of targeted therapies for patients with pancreatic ductal adenocarcinoma?
- How can the insights gained from current research on pancreatic cancer inform future clinical practices in early diagnosis and treatment?
Key Findings
Research Background and Objectives
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor prognosis, primarily due to late-stage diagnosis and resistance to therapy. The incidence of PDAC is increasing, influenced by various modifiable and non-modifiable risk factors such as chronic pancreatitis, diabetes, smoking, obesity, and genetic predisposition. This study aims to explore advancements in early detection, treatment strategies, and emerging therapeutic approaches for PDAC.
Main Methods/Materials/Experimental Design
The research involves a comprehensive review of current literature on PDAC, focusing on diagnostic techniques and treatment options. The methodology encompasses:
- Literature Review: Analysis of studies on biomarkers, imaging techniques, and treatment regimens.
- Clinical Strategies: Evaluation of surgical options, neoadjuvant therapies, and novel drug combinations.
The following flowchart summarizes the key methodologies:
Key Results and Findings
- Early Detection: Improved imaging and biomarker identification can potentially enhance early diagnosis in high-risk groups.
- Surgical Resection: Only 15%-20% of patients present with resectable disease at diagnosis.
- Neoadjuvant Chemotherapy: This strategy has shown promise in increasing resectability and improving survival.
- Combination Chemotherapy: Regimens like FOLFIRINOX and NALIRIFOX have demonstrated survival benefits, although they are associated with significant toxicity.
- Targeted Therapies: Advances in molecular profiling have led to the introduction of drugs such as sotorasib and olaparib.
- Immunotherapy Challenges: Limited success in PDAC due to the immunosuppressive tumor microenvironment, but new combination strategies are being tested.
Main Conclusions/Significance/Innovation
The study underscores the critical need for improved early detection methods and innovative treatment strategies to combat PDAC. While surgical resection remains the most effective curative option, advancements in neoadjuvant therapies and targeted treatments are paving the way for better patient outcomes. The exploration of combination therapies and personalized medicine represents a significant shift in the management of this malignancy.
Research Limitations and Future Directions
- Limitations: The review highlights the challenges in achieving early diagnosis and the high toxicity associated with current chemotherapeutic regimens. Additionally, the effectiveness of immunotherapy remains limited due to the tumor microenvironment.
- Future Directions:
- Identification of reliable biomarkers for early detection.
- Refinement of patient selection for targeted therapies.
- Development of innovative strategies to overcome treatment resistance, including personalized neoantigen vaccines and novel combination therapies.
| Aspect | Current Status | Future Focus |
|---|---|---|
| Early Detection | Limited efficacy of current biomarkers and imaging | Reliable biomarker identification |
| Treatment Strategies | Surgical resection and combination chemotherapy | Targeted therapy refinement |
| Immunotherapy | Limited success due to tumor microenvironment | Combination approaches and novel strategies |
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