{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:29:06Z","timestamp":1789421346481,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTCs) remain highly lethal gastrointestinal malignancies because of late presentation, marked molecular heterogeneity, and limited durable benefit from conventional systemic therapy. This narrative review summarizes recent advances in both diseases, focusing on practice-informing clinical trials, biomarker-driven treatment strategies, and translational insights into tumor biology and resistance. In PDAC, progress includes refinement of perioperative management, broader germline and somatic testing, recognition of DNA damage repair-deficient subsets, and development of KRAS-directed therapies and rational combination strategies. In BTCs, especially intrahepatic cholangiocarcinoma, comprehensive molecular profiling has expanded precision oncology through actionable alterations such as FGFR2 rearrangements, IDH1 mutations, HER2 amplification\/overexpression, BRAF V600E, NTRK fusions, and MSI-high\/dMMR status. Immunotherapy has a clearer role in selected BTC populations, whereas in PDAC benefit remains largely restricted to rare biomarker-defined subsets. Across both diseases, circulating tumor DNA is emerging as a promising tool for prognostication, minimal residual disease assessment, response monitoring, and early resistance detection. Contemporary care increasingly depends on early molecular profiling, individualized treatment sequencing, and integration of targeted therapies, biomarker-guided immunotherapy, and clinical trials.<\/jats:p>","DOI":"10.3390\/ijms27104413","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:33:21Z","timestamp":1778841201000},"page":"4413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Recent Advances in Pancreatic Cancer and Biliary Tract Cancers: Biology, Biomarkers, and Evolving Systemic Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9062-9761","authenticated-orcid":false,"given":"Ehab","family":"Takrori","sequence":"first","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Abdulmajid","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepthi","family":"Devagudi","sequence":"additional","affiliation":[{"name":"Department of Hospital Medicine, Adventist Health, Hanford, CA 93230, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramsha","family":"Sohail","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Norton Community Hospital, Norton, VA 24273, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaynah","family":"Sadiq","sequence":"additional","affiliation":[{"name":"Washington Health, Fremont, CA 94538, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Berneau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Norton Community Hospital, Norton, VA 24273, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Shenouda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Norton Community Hospital, Norton, VA 24273, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4516-7626","authenticated-orcid":false,"given":"Rakesh","family":"Adelli","sequence":"additional","affiliation":[{"name":"Center for Applied Research and Evaluation in Women\u2019s Health, Department of Health Services Management & Policy, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-9474","authenticated-orcid":false,"given":"Supriya","family":"Peshin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Norton Community Hospital, Norton, VA 24273, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakshi","family":"Singal","sequence":"additional","affiliation":[{"name":"Department of Hematology & Oncology, East Tennessee State University, Johnson City, TN 37604, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","first-page":"144","article-title":"Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future","volume":"76","author":"Mannucci","year":"2026","journal-title":"CA Cancer J. 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