Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains one of the most lethal malignancies, characterized by late diagnosis, aggressive tumor biology, and profound resistance to conventional therapies. Despite advances in surgical techniques and combination chemotherapy regimens such as FOLFIRINOX and gemcitabine-based therapies, survival outcomes remain poor, with five-year survival rates barely exceeding 10%. Recent progress in molecular oncology has provided critical insights into the genomic landscape of PDAC, highlighting key driver mutations, particularly in KRAS, as well as alterations in tumor suppressor genes including TP53, CDKN2A, and SMAD4. These discoveries have catalyzed the development of precision oncology approaches aimed at tailoring treatment based on individual tumor biology. Emerging therapeutic strategies include direct targeting of KRAS mutations, exploitation of DNA damage repair deficiencies using PARP inhibitors, and the integration of biomarker-driven treatment selection. Concurrently, novel diagnostic modalities such as liquid biopsy and exosome-based biomarkers offer non-invasive methods for real-time disease monitoring and early detection. Advances in artificial intelligence and multi-omics integration further enhance the ability to interpret complex biological data and guide personalized therapeutic decisions. This Narrative review synthesizes current evidence on the molecular drivers of pancreatic cancer and explores emerging precision oncology strategies, emphasizing the transition from conventional treatment paradigms toward adaptive, biomarker-guided approaches. The integration of molecular diagnostics, targeted therapies, and computational tools represents a promising pathway toward improving clinical outcomes in this highly aggressive disease.

Pancreatic ductal adenocarcinoma (PDAC), Precision oncology, KRAS mutations, Liquid biopsy, Tumor microenvironment