Precision Therapeutics in Pancreatic Cancer: Emerging Targeted, Immune, and Antibody-Drug Conjugate Strategies Exemplified by Adagrasib, Dostarlimab, and Trastuzumab Deruxtecan.

Pancreatic cancer remains one of the most aggressive and lethal malignancies, characterized by late-stage diagnosis, profound molecular heterogeneity, and limited responsiveness to conventional cytotoxic therapies. Recent advances in molecular diagnostics and biomarker-driven treatment stratification have accelerated the development of precision therapeutic approaches aimed at improving outcomes in selected patient populations. This review highlights three mechanistically distinct yet complementary therapeutic strategies that illustrate the evolving landscape of personalized pancreatic cancer management. Adagrasib represents targeted inhibition of oncogenic KRAS G12C signaling, reflecting recent progress in directly targeting historically "undruggable" driver mutations. Dostarlimab illustrates the tissue-agnostic application of immune checkpoint blockade in pancreatic cancers harboring mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), highlighting the growing importance of biomarker-defined immunotherapy-responsive subsets despite the limited pancreatic cancer-specific clinical evidence currently available. Trastuzumab deruxtecan represents a next-generation HER2-directed antibody-drug conjugate (ADC) and demonstrates the potential of HER2-targeted therapy in the small subgroup of patients with HER2-positive pancreatic cancer, although the available evidence is derived primarily from basket trials and tumor-agnostic clinical development. Collectively, these therapeutic approaches underscore the expanding role of biomarker-guided treatment strategies integrating targeted inhibition, immunotherapy, and precision cytotoxic payload delivery. This review summarizes the molecular rationale, available clinical evidence, therapeutic limitations, and resistance mechanisms associated with these approaches while discussing emerging directions in translational research, rational combination strategies, liquid biopsy applications, and precision oncology that may further refine individualized treatment algorithms for pancreatic cancer.