[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-353215-105":59,"doc-detail-353215-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","pancreatic-cancer-translating-tumor-biology-into-actionability-review","Pancreatic Cancer - Translating Tumor Biology into Actionability - Review","","Pancreatic ductal adenocarcinoma (PDAC) represents the majority of pancreatic cancers and is associated with poor prognosis. A minority of patients present with resectable disease, while additional cases can be downstaged to enable surgery. Management across stages relies on chemotherapy, with targeted therapies for select actionable genomic alterations. The review emphasizes how tumor microenvironment biology and recent advances are shaping emerging targeted and immunomodulatory treatment paradigms.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pancreatic-cancer-translating-tumor-biology-into-actionability-review/353215/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/pancreatic-cancer-translating-tumor-biology-into-actionability-review/353215.png","ImageObject",300,407,{"name":92,"@type":93},"Bulrr","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What proportion of pancreatic ductal adenocarcinoma is resectable at diagnosis, and what happens with downstaging?","Question",{"text":113,"@type":114},"About 10% to 15% of cases are resectable at diagnosis. An additional 5% to 15% can be downstaged with therapy to a point where surgery becomes feasible.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which treatment approach is described as a mainstay for all stages of PDAC?",{"text":118,"@type":114},"Chemotherapy is described as the mainstay across all stages of PDAC.",{"name":120,"@type":111,"acceptedAnswer":121},"How does the review relate the tumor microenvironment to treatment resistance in PDAC?",{"text":122,"@type":114},"It describes a dense stroma with an immunosuppressive milieu that contributes to inherent treatment resistance in PDAC.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},353215,1790862715,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","review  \nPancreatic Cancer: Translating Tumor Biology  \ninto Actionability   \nFiyinfolu O. Balogun1,2, 3, Mara H. Sherman2,4, Wungki Park1,2, 3, Kevin C. Soares2, 5, Marsha Reyngold2, 6, Joshua D. Schoenfeld1,2, Anupriya Singhal1,2, Christine A. Iacobuzio-Donahue2,7, and Eileen M. O’Reilly1,2, 3  \nPancreatic ductal adenocarcinoma (PDAC) accounts for 90% of pancreatic cancers  \nand has a very poor prognosis. Ten to 15% are staged as resectable at diagnosis, and 5% to 15% downstaged with therapy to where surgery is feasible. Chemotherapy is a mainstay for all stages of PDAC. Targeted therapies are available for patients with select but expanding actionable genomic alterations. The tumor microenvironment provides a dense stroma with an immunosuppressive milieu that contributes to inherent treatment resistance of PDAC. Herein, we review current management of PDAC with a focus on emerging treatment paradigms, including targeted and immunomodulatory agents.  \nSignificance: PDAC is a complex disease with unique genomic, immunologic, and clinical features. Recent developments in understanding of the pathobiology of this disease are translating into targeted and immunomodulatory therapies that will alter treatment paradigms and improve outcomes for this recalcitrant malignancy.  \nCurrent treatment Paradigms  \nEarly-Stage Disease  \nApproximately 15% to 20% of PDAC are resectable at diagnosis, with multimodality therapy maximizing the chances of an optimal outcome. Perioperative treatment typically includes 6 months of cytotoxic therapy (Table 1). The CONKO (Charité Onkologie)-001 study identified gemcitabine as a recommended single agent with improvement in median overall survival [mOS; HR, 0.76; 95% confidence interval (CI), 0.61–0.95; P = 0.01; ref. 1]. The ESPAC-4 trial established the benefit of  \n1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 2David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York.  \n3Department of Medicine, Weill Cornell Medicine, New York, New York.  \n4Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York. 5Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. 6Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 7Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.  \nCorresponding Author: Eileen M. O’Reilly, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 E 66th Street, 1041, New York, NY  \n10065. E-mail: [oreillye@mskcc.org](oreillye@mskcc.org)  \nCancer Discov 2026;16:1262–79  \ndoi: 10. 1158/2159-8290 . CD-25-2014  \nThis open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.  \n©2026 The Authors; Published by the American Association for Cancer Research  \nmulti-agent therapy, with gemcitabine plus capecitabine demonstrating superiority over single-agent gemcitabine (mOS HR, 0.83; 95% CI, 0.71–0.98; P = 0.031; ref. 2) . The PRODIGE (Partenariat de Recherche en Oncologie Digestive)-24 trial identified FOLFIRINOX [5-fluorouracil (5-FU), oxaliplatin, irinotecan, and leucovorin (LV)] as the standard adjuvant regimen for patients with Eastern Cooperative Oncology Group (ECOG) 0 to 1, demonstrating median disease-free survival (DFS) of 21.6 months compared with 12.8 months in gemcitabine (HR, 0.58; 95% CI, 0.46–0.73; P \u003C 0.001; ref. 3) . Gemcitabine/nab-paclitaxel was explored as adjuvant therapy in the randomized phase III APACT (Adjuvant Pancreatic Adenocarcinoma Clinical Trial) study, where it was not found tobe superior to gemcitabine monotherapy in the primary endpoint of DFS (HR, 0.88; 95% CI, 0.73–1.06; P = 0.18; ref. 4) . A significant benefit in OS, a secondary endpoint, was noted with 40.5 months for gemcitabine/nab-paclitaxel and 36.2 months","cbCaic4uqYBL1cRQ","https://ap.wps.com/l/cbCaic4uqYBL1cRQ","pdf",5559767,18,"English","# Significance\n# Current treatment Paradigms\n## Early-Stage Disease\n## Therapy Sequencing in Early-Stage Disease—Neoadjuvant Versus Adjuvant","[{\"question\":\"What proportion of pancreatic ductal adenocarcinoma is resectable at diagnosis, and what happens with downstaging?\",\"answer\":\"About 10% to 15% of cases are resectable at diagnosis. An additional 5% to 15% can be downstaged with therapy to a point where surgery becomes feasible.\"},{\"question\":\"Which treatment approach is described as a mainstay for all stages of PDAC?\",\"answer\":\"Chemotherapy is described as the mainstay across all stages of PDAC.\"},{\"question\":\"How does the review relate the tumor microenvironment to treatment resistance in PDAC?\",\"answer\":\"It describes a dense stroma with an immunosuppressive milieu that contributes to inherent treatment resistance in PDAC.\"}]","Pancreatic Cancer - Translating Tumor Biology into Actionability - Review | PDF",1790103616,45]