{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:03:34Z","timestamp":1790615014609,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: PDAC is a highly aggressive malignancy driven predominantly by activating KRAS mutations, and allele-specific and pan-RAS inhibitors have emerged as candidate targeted therapies. Evidence supporting them is dominated by experimental studies of which the models differ widely in how faithfully they reproduce human disease, and clinical maturity is uneven across alleles. Objectives: The objective of this study was to evaluate allele-stratified RAS-inhibitor activity across KRAS subtypes in PDAC, synthesizing experimental and clinical evidence separately, and determine whether the principal conclusions of the review survive when the experimental evidence is stratified by the level of model validation achieved. Methods: PubMed, Cochrane Library, Scopus, and Google Scholar were searched from inception to 26 June 2026, with a pre-specified updated search in June 2026. Experimental studies were appraised with a modified JBI Critical Appraisal Checklist for Quasi-Experimental Studies supplemented by preclinical-specific reporting domains, and were independently classified by the highest level of model validation achieved, from conventional two-dimensional cell lines through to multi-model validation spanning patient-derived and immunocompetent in vivo systems; clinical studies were appraised with ROBINS-I. Experimental and clinical evidence was synthesized separately. Single-arm proportions from KRAS G12C trials were pooled on the logit scale using inverse-variance random-effects meta-analysis with Hartung\u2013Knapp confidence intervals, and certainty was rated using GRADE. Results: Twenty-four studies were included (twenty experimental and four early-phase, single-arm clinical trials). Four of the twenty experimental studies (20%) rested on conventional two-dimensional cell lines alone, nine (45%) incorporated patient-derived material, seven (35%) used immunocompetent models, and fourteen (70%) reproduced their principal finding in at least two independent model classes. The allele-dependent pattern of single-agent activity persisted when cell-line-only studies were set aside, whereas 6 of the 17 studies reporting combination strategies provided no confirmation in any higher-order system. Across three single-arm KRAS G12C trials, the pooled objective response rate was 36.9% (95% CI, 9.8\u201375.7%; I2 = 66.2%; individual trials 21.1%, 45.5%, and 46.9%), the pooled disease control rate was 85.9% (95% CI, 62.1\u201395.8%; I2 = 0%; individual datasets 81.8%, 84.2%, and 93.8%), and the grade \u2265 3 treatment-related adverse event rate was 23.8% (95% CI, 11.2\u201343.5%; I2 = 0%). GRADE certainty was very low for all three outcomes. Conclusions: The available evidence is consistent with allele-dependent activity of RAS-targeted therapy in PDAC and supports biomarker-guided treatment selection, but the clinical evidence base is confined to small, single-arm, early-phase trials of KRAS G12C inhibitors. The pooled estimates are exploratory descriptions of observed activity in selected early-phase populations, not comparative estimates of treatment efficacy. KRAS G12D-directed therapy remains at a substantially earlier stage of clinical validation than KRAS G12C-directed therapy despite a much larger preclinical literature.<\/jats:p>","DOI":"10.3390\/cancers18193139","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:57:57Z","timestamp":1790611077000},"page":"3139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Allele-Stratified Activity of RAS Inhibitors in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Exploratory Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1221-9921","authenticated-orcid":false,"given":"Munahil Ilyas","family":"Muhammad","sequence":"first","affiliation":[{"name":"College of Medicine, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-1845","authenticated-orcid":false,"given":"Aisha","family":"Al-Khinji","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8088-6408","authenticated-orcid":false,"given":"Mayasa","family":"Al-Ansari","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8028-6840","authenticated-orcid":false,"given":"Najlaa","family":"Al-Marri","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9179-7979","authenticated-orcid":false,"given":"Shahad","family":"Al-Shaheen","sequence":"additional","affiliation":[{"name":"College of Medicine, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-7141","authenticated-orcid":false,"given":"Dhafer","family":"Malouche","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, College of Arts and Sciences, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.3748\/wjg.v24.i43.4846","article-title":"Pancreatic cancer: A Review of Clinical diagnosis, epidemiology, Treatment and Outcomes","volume":"24","author":"McGuigan","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"zrac004","DOI":"10.1093\/bjsopen\/zrac004","article-title":"Treatment and survival of patients with pancreatic ductal adenocarcinoma: 15-year national cohort","volume":"6","author":"Nymo","year":"2022","journal-title":"BJS Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.gie.2024.03.023","article-title":"Assessing EUS-guided radiofrequency ablation in unresectable pancreatic ductal adenocarcinoma: A single-center historic cohort study","volume":"100","author":"Valle","year":"2024","journal-title":"Gastrointest. Endosc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103375","DOI":"10.1016\/j.redox.2024.103375","article-title":"A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer","volume":"77","author":"Bodeker","year":"2024","journal-title":"Redox Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1158\/1078-0432.CCR-21-3581","article-title":"Molecular characterization of KRAS wild type tumors in patients with pancreatic adenocarcinoma","volume":"28","author":"Philip","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"de Jesus, V.H.F., Mathias-Machado, M.C., de Farias, J.P.F., Aruquipa, M.P.S., J\u00e1come, A.A., and Peixoto, R.D. (2023). Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure. Cancers, 15.","DOI":"10.3390\/cancers15205015"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/JP9.0000000000000244","article-title":"Development of targeted therapy for pancreatic ductal adenocarcinoma: A 5-year review","volume":"9","author":"Zhou","year":"2025","journal-title":"J. Pancreatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1200\/JCO.2025.43.4_suppl.724","article-title":"Preliminary safety, antitumor activity, and circulating tumor DNA (ctDNA) changes with RMC-9805, an oral, RAS(ON) G12D-selective tri-complex inhibitor in patients with KRAS G12D pancreatic ductal adenocarcinoma (PDAC) from a phase 1 study in advanced solid tumors","volume":"43","author":"Spira","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liu, Y., Cheng, Y., Huang, G., Xia, X., Wang, X., and Tian, H. (2023). Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1271268"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"799","DOI":"10.32604\/or.2024.045356","article-title":"Targeting KRAS in pancreatic cancer","volume":"32","author":"Stickler","year":"2024","journal-title":"Oncol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2453588","DOI":"10.1001\/jamanetworkopen.2024.53588","article-title":"KRAS Mutation Status and Treatment Outcomes in Patients with Metastatic Pancreatic Adenocarcinoma","volume":"8","author":"Norton","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Linehan, A., O\u2019Reilly, M., McDermott, R., and O\u2019Kane, G.M. (2024). Targeting KRAS mutations in pancreatic cancer: Opportunities for future strategies. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1369136"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41698-024-00505-0","article-title":"Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma","volume":"8","author":"Yousef","year":"2024","journal-title":"npj Precis. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/s41591-024-03362-3","article-title":"Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival","volume":"31","author":"Varghese","year":"2025","journal-title":"Nat. Med."},{"key":"ref_15","first-page":"12","article-title":"Pancreatic cancer therapy in the era of precision oncology","volume":"2","year":"2026","journal-title":"Clin. Res. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2014.12.021","article-title":"Organoid models of human and mouse ductal pancreatic cancer","volume":"160","author":"Boj","year":"2015","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1158\/2159-8290.CD-18-0349","article-title":"Organoid profiling identifies common responders to chemotherapy in pancreatic cancer","volume":"8","author":"Tiriac","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"372.","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Methley, A.M., Campbell, S., Chew-Graham, C., McNally, R., and Cheraghi-Sohi, S. (2014). PICO, PICOS and SPIDER: A Comparison Study of Specificity and Sensitivity in Three Search Tools for Qualitative Systematic Reviews. BMC Health Serv. Res., 14.","DOI":"10.1186\/s12913-014-0579-0"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Moola, S., Munn, Z., Tufanaru, C., Aromataris, E., Sears, K., Sfetc, R., Currie, M., Lisy, K., Qureshi, R., and Mattis, P. (2020). Chapter 7: Systematic Reviews of Etiology and Risk. JBI Man. Evid. Synth.","DOI":"10.46658\/JBIRM-17-06"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hooijmans, C.R., Rovers, M.M., de Vries, R.B.M., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M.W. (2014). SYRCLE\u2019s risk of bias tool for animal studies. BMC Med. Res. Methodol., 14.","DOI":"10.1186\/1471-2288-14-43"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1002\/cac2.70056","article-title":"Efficacy and safety of glecirasib in solid tumors with KRAS G12C mutation: A pooled analysis of two phase I\/II trials","volume":"45","author":"Li","year":"2025","journal-title":"Cancer Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1056\/NEJMoa2600752","article-title":"Setidegrasib in Advanced Non\u2013Small-Cell Lung Cancer and Pancreatic Cancer","volume":"394","author":"Park","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1056\/NEJMoa2208470","article-title":"Sotorasib in KRAS p.G12C\u2013Mutated advanced pancreatic cancer","volume":"388","author":"Strickler","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41416-025-03286-w","article-title":"Efficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer","volume":"134","author":"Yamamoto","year":"2025","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1158\/2159-8290.CD-24-0177","article-title":"Mechanisms of resistance to oncogenic KRAS inhibition in pancreatic cancer","volume":"14","author":"Dilly","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102421","DOI":"10.1016\/j.tranon.2025.102421","article-title":"KRAS inhibition reverses chemotherapy resistance promoted by therapy-induced senescence-like in pancreatic ductal adenocarcinoma","volume":"57","author":"Abuelafia","year":"2025","journal-title":"Transl. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.actbio.2025.12.049","article-title":"Dual Inhibition of KRAS G12D and PI3K\/BRD4 signaling overcomes therapeutic resistance in pancreatic cancer","volume":"212","author":"Ghanwatkar","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1038\/s41591-022-02007-7","article-title":"Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor","volume":"28","author":"Hallin","year":"2022","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"217258","DOI":"10.1016\/j.canlet.2024.217258","article-title":"Macroautophagy\/autophagy promotes resistance to KRASG12D-targeted therapy through glutathione synthesis","volume":"604","author":"Han","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jesenko, T., Omerzel, M., Zivic, T., Sersa, G., and Cemazar, M. (2025). In Vitro Evaluation of Electrochemotherapy Combined with Sotorasib in Pancreatic Carcinoma Cell Lines Harboring Distinct KRAS Mutations. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157165"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101966","DOI":"10.1016\/j.xcrm.2025.101966","article-title":"KRASG12D-driven pentose phosphate pathway remodeling imparts a targetable vulnerability synergizing with MRTX1133 for durable remissions in PDAC","volume":"6","author":"Jiang","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1158\/0008-5472.CAN-23-2504","article-title":"The extracellular niche and tumor microenvironment enhance KRAS inhibitor efficacy in pancreatic cancer","volume":"84","author":"Kumarasamy","year":"2024","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ma, Y., Schulz, B., Trakooljul, N., Al Ammar, M., Sekora, A., Sender, S., Hadlich, F., Zechner, D., Weiss, F.U., and Lerch, M.M. (2022). Inhibition of KRAS, MEK and PI3K Demonstrate Synergistic Anti-Tumor Effects in Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers, 14.","DOI":"10.3390\/cancers14184467"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.ccell.2023.07.002","article-title":"KRASG12D inhibition reprograms the microenvironment of early and advanced pancreatic cancer to promote FAS-mediated killing by CD8+ T cells","volume":"41","author":"Mahadevan","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/1878-0261.13751","article-title":"Targeting KRAS-mutant pancreatic cancer through simultaneous inhibition of KRAS, MEK, and JAK2","volume":"19","author":"Miyazaki","year":"2024","journal-title":"Mol. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Moln\u00e1r, E., Baranyi, M., Szigeti, K., Heged\u0171s, L., Bord\u00e1s, F., G\u00e1briel, Z., Pet\u00e9nyi, G., T\u00f3v\u00e1ri, J., Heged\u0171s, B., and T\u00edm\u00e1r, J. (2024). Combination of farnesyl-transferase inhibition with KRAS G12D targeting breaks down therapeutic resistance in pancreatic cancer. Pathol. Oncol. Res., 30.","DOI":"10.3389\/pore.2024.1611948"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5246","DOI":"10.1158\/1078-0432.CCR-25-2333","article-title":"Targeting KRAS Inhibitor-Resistant Pancreatic Cancer with an MUC1-C Antibody-Drug Conjugate","volume":"31","author":"Ozawa","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41419-025-08362-w","article-title":"Simultaneous targeting of KRAS and CDK4 synergistically induces durable growth arrest in pancreatic cancer cells","volume":"17","author":"Paulsohn","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1158\/1535-7163.MCT-25-0483","article-title":"Resistance to the KRASG12D Inhibitor MRTX1133 is Associated with Increased Sensitivity to BET Inhibition","volume":"25","author":"Principe","year":"2026","journal-title":"Mol. Cancer Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ramalingam, P.S., Chellasamy, G., Hussain, M.S., Kodiveri Muthukaliannan, G., Hussain, T., Alrokayan, S., Yun, K., Mekala, J.R., and Arumugam, S. (2025). Synergistic anticancer effects of camptothecin and sotorasib in KRAS-mutated pancreatic ductal adenocarcinoma. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1635449"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eadq4274","DOI":"10.1126\/sciadv.adq4274","article-title":"SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition","volume":"10","author":"Song","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1038\/s41598-025-34204-y","article-title":"Antimetastatic effects of MRTX1133 KRAS G12D specific inhibitor in a liver metastatic model of pancreatic ductal adenocarcinoma","volume":"16","author":"Szigeti","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4523","DOI":"10.62347\/DVXL1377","article-title":"Synergistic anti-tumor activity, reduced pERK, and immuno-stimulatory cytokine profiles with 5-FU or ONC212 plus KRAS G12D inhibitor MRTX1133 in CRC and pancreatic cancer cells independent of G12D mutation","volume":"14","author":"Tajiknia","year":"2024","journal-title":"Am. J. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1038\/s41467-026-69695-4","article-title":"Combination of PARP and KRASG12D inhibitors enhances therapeutic efficacy by exploiting vulnerabilities in PDAC","volume":"17","author":"Xu","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/17439760.2016.1262613","article-title":"Thematic analysis","volume":"12","author":"Clarke","year":"2017","journal-title":"J. Posit. Psychol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Borenstein, M. (2022). Comprehensive meta-analysis software. Systematic Reviews in Health Research: Meta-Analysis in Context, John Wiley & Sons.","DOI":"10.1002\/9781119099369.ch27"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1136\/bmj.39489.470347.AD","article-title":"GRADE: An emerging consensus on rating quality of evidence and strength of recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1056\/NEJMoa2505783","article-title":"Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer","volume":"394","author":"Wolpin","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1056\/NEJMoa2605555","article-title":"Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer","volume":"395","author":"Wainberg","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.21037\/tcr-23-1629","article-title":"KRAS G12C inhibitors: Also a new promising new targeted therapy in advanced pancreatic adenocarcinoma?","volume":"12","author":"Muller","year":"2023","journal-title":"Transl. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103123","DOI":"10.1016\/j.ctrv.2026.103123","article-title":"Targeted therapeutic strategies in rare subtypes of pancreatic cancer: Histology, molecular profiles, and emerging opportunities","volume":"145","author":"Scarlato","year":"2026","journal-title":"Cancer Treat. Rev."},{"key":"ref_55","unstructured":"Amgen, I. (2024). LUMAKRAS (Sotorasib) Tablets, for Oral Use: US Prescribing Information, Amgen Inc."},{"key":"ref_56","unstructured":"Mirati Therapeutics, Inc. (2024). KRAZATI (Adagrasib) Tablets, for Oral Use: US Prescribing Information, Mirati Therapeutics, Inc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1021\/acs.jmedchem.1c01688","article-title":"Identification of MRTX1133, a noncovalent, potent, and selective KRAS G12D inhibitor","volume":"65","author":"Wang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sena, E.S., van der Worp, H.B., Bath, P.M.W., Howells, D.W., and Macleod, M.R. (2010). Publication bias in reports of animal stroke studies leads to major overstatement of efficacy. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000344"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nusrat, F., Khanna, A., Jain, A., Jiang, W., Lavu, H., Yeo, C.J., Bowne, W., and Nevler, A. (2024). The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma. J. Clin. Med., 13.","DOI":"10.3390\/jcm13072103"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Bannoura, S.F., Khan, H.Y., and Azmi, A.S. (2022). KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1013902"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12032-025-02683-8","article-title":"Enhancing KRAS G12D inhibitor sensitivity in pancreatic cancer through SHP2\/PI3K pathway","volume":"42","author":"Hao","year":"2025","journal-title":"Med. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:10:21Z","timestamp":1790611821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":61,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cancers18193139"],"URL":"https:\/\/doi.org\/10.3390\/cancers18193139","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]}}}