{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T16:43:57Z","timestamp":1792341837590,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) remains among the most lethal malignancies, and activating\n                    <jats:italic>KRAS<\/jats:italic>\n                    mutations occur in more than 90% of tumors. Direct\n                    <jats:italic>RAS<\/jats:italic>\n                    targeting has moved from proof of concept to randomized clinical benefit: in previously treated metastatic PDAC, daraxonrasib improved median overall survival, progression\u2010free survival, and objective response rate versus chemotherapy. Mutation\u2010selective G12C and G12D inhibitors, targeted degraders, and first\u2010line\n                    <jats:italic>RAS<\/jats:italic>\n                    (ON) combinations further broaden the landscape. Comprehensive germline and somatic profiling remains essential even with the availability of multi\u2010selective\n                    <jats:italic>KRAS<\/jats:italic>\n                    inhibitors.\n                    <jats:italic>KRAS<\/jats:italic>\n                    alleles differ biologically, drug activity against individual alleles is not yet fully characterized, and eligibility for clinical trials often depends on the specific genotype. In addition,\n                    <jats:italic>KRAS<\/jats:italic>\n                    wild\u2010type tumors may harbor actionable alterations, including gene fusions, amplifications, or mismatch\u2010repair deficiency. This review synthesizes\n                    <jats:italic>RAS<\/jats:italic>\n                    biology, molecular\u2010testing implications, clinical efficacy and toxicity data, and ongoing phase 2 and phase 3 trials. Priority questions include optimal sequencing, management of rash and mucositis, resistance, biomarker development, and integration into first\u2010line and curative\u2010intent therapy.\n                  <\/jats:p>","DOI":"10.1002\/cncr.70640","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:07:17Z","timestamp":1791292037000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting\n                    <i>RAS<\/i>\n                    in pancreatic cancer"],"prefix":"10.1002","volume":"132","author":[{"given":"Fausto","family":"Petrelli","sequence":"first","affiliation":[{"name":"Oncology Unit ASST Bergamo Ovest  Treviglio Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Dottorini","sequence":"additional","affiliation":[{"name":"Oncology Unit ASST Bergamo Ovest  Treviglio Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Zaniboni","sequence":"additional","affiliation":[{"name":"Oncology Unit Fondazione Poliambulanza  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.014"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17152453"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a031435"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00334-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.02.037"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010022\u201000671\u20109"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1011923"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1304369"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00986-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1903387"},{"key":"e_1_2_8_13_1","first-page":"889","article-title":"The role of germline testing and PARP inhibition in pancreatic cancer","volume":"24","author":"Golan T","year":"2022","journal-title":"Curr Oncol Rep"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-24-0027"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007205\u20106"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2605555"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2505783"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201019\u20101006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2026.44.16_suppl.tps4264"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1917239"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2208470"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.23.00434"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.cd\u201024\u20100177"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201002007\u20107"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01688"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2600752"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004\u2010025\u201001662\u20104"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28145600"},{"key":"e_1_2_8_29_1","unstructured":"US Food and Drug Administration.FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma. 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Version 2.2026.https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010approves\u2010daraxonrasib\u2010metastatic\u2010pancreatic\u2010adenocarcinoma"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.am2026\u2010lb337"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.am2026\u2010lb407"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.05.381"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.05.382"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006123\u20103"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.08.003"},{"key":"e_1_2_8_36_1","unstructured":"National Comprehensive Cancer Network.NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma; Version 2.2025.https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/pancreatic.pdf"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.01364"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.08.009"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1013902"},{"key":"e_1_2_8_40_1","unstructured":"US Food and Drug Administration.FDA permits expanded access for investigational pancreatic cancer drug. 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