Advancing Precision Medicine in PDAC: An Ethical Scoping Review and Call to Action for IHC Implementation

Area of Science:

• Oncology
• Pathology
• Biomarker Research

Background:

• Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges.
• Predictive biomarkers are crucial for improving diagnosis, prevention, and treatment, especially preoperatively.
• Ethical considerations are paramount for implementing new biomarkers in clinical practice.

Purpose of the Study:

• To conduct a scoping review on the ethical landscape of using immunohistochemistry (IHC) for molecular subtyping in PDAC.
• To analyze the utility, accessibility, and impact of IHC as a companion diagnostic tool.
• To evaluate the ethical dimensions of IHC-based molecular subtyping in PDAC.

Main Methods:

• Systematic literature search across PubMed, Scopus, and Google Scholar (2015-2025) using COVIDENCE.
• Identification and review of 130 references, with 9 ultimately meeting inclusion criteria.
• Analysis focused on IHC's advantages over complex molecular methods and its ethical implications.

Main Results:

• IHC is a cost-effective, widely available companion diagnostic tool, easily integrated into clinical workflows.
• Protein-level assessment via IHC is often more accurate than mRNA analysis for biomarker regulation.
• Standardized IHC protocols are essential for translating molecular subtyping into actionable treatment strategies for PDAC, including aggressive subtypes.

Conclusions:

• IHC-driven molecular subtyping offers a practical approach to optimize therapy selection in PDAC.
• This method maximizes patient benefits and minimizes exposure to ineffective treatments.
• Equitable and responsible access to IHC-based precision oncology is urged for all PDAC patients.