KRAS突变肿瘤的药物治疗研究进展
Research Progress in Drug Therapy for KRAS-Mutant Tumors
DOI: 10.12677/wjcr.2026.163023, PDF,    科研立项经费支持
作者: 金石林*, 王露妍*：昆明医科大学药学院暨云南省天然药物药理重点实验室，云南 昆明；梁蕾蕾#：昆明医科大学基础医学院，云南 昆明
关键词: KRAS突变；肿瘤药物治疗；靶向治疗；免疫治疗；联合治疗；KRAS Mutation； Tumor Pharmacotherapy； Targeted Therapy； Immunotherapy； Combination Therapy
摘要: KRAS突变是肺癌、结直肠癌、胰腺癌等多种实体肿瘤的关键驱动事件，不同突变亚型在生物学行为和治疗反应上呈现高度异质性。针对KRAS突变肿瘤的药物治疗主要包括靶向治疗、免疫治疗等。KRASG12C抑制剂的问世标志着靶向治疗取得突破性进展，非G12C亚型、泛KRAS及相关信号通路的干预药物也在持续研发中，免疫治疗同样展现出临床应用潜力。然而，单一疗法的疗效受多种因素限制，整合多靶点、多通路抑制并联合免疫治疗的策略正成为重要的发展方向。文章围绕KRAS突变的肺癌、结直肠癌和胰腺癌，对药物靶向治疗、免疫治疗及联合治疗的研究进展进行综述，并总结应用进展、面临挑战及新兴疗法，以期为促进KRAS突变肿瘤药物治疗发展提供参考。
Abstract: KRAS mutation serves as a critical oncogenic driver event in multiple solid tumors, including lung cancer, colorectal cancer, and pancreatic cancer. Different KRAS mutation subtypes exhibit high heterogeneity in biological behavior and therapeutic response. Pharmacological interventions for KRAS-mutant tumors primarily comprise targeted therapy and immunotherapy. The development of KRASG12C inhibitors has marked a breakthrough in targeted therapy, while therapeutic strategies targeting non-G12C subtypes, pan-KRAS, and related signaling pathways are advancing. Immunotherapy has also demonstrated clinical potential. Nevertheless, the efficacy of monotherapy is constrained by multiple factors. The combination therapy integrating multi-target, multi-pathway inhibition with immunotherapy has emerged as a direction. This article reviews the advances, challenges, and emerging therapies in targeted therapy, immunotherapy, and combination therapy for KRAS-mutant tumors, aiming to facilitate the development of pharmacological treatments.
文章引用：金石林, 王露妍, 梁蕾蕾. KRAS突变肿瘤的药物治疗研究进展[J]. 世界肿瘤研究, 2026, 16(3): 218-231. https://doi.org/10.12677/wjcr.2026.163023

参考文献

[1] Klomp, J.E., Diehl, J.N., Klomp, J.A., Edwards, A.C., Yang, R., Morales, A.J., et al. (2024) Determining the ERK-Regulated Phosphoproteome Driving Kras-Mutant Cancer. Science, 384, eadk0850. [Google Scholar] [CrossRef] [PubMed]
[2] Xu, L., Ding, R., Song, S., Liu, J., Li, J., Ju, X., et al. (2024) Single‐Cell RNA Sequencing Reveals the Mechanism of PI3K/Akt/mTOR Signaling Pathway Activation in Lung Adenocarcinoma by KRAS Mutation. The Journal of Gene Medicine, 26, e3658. [Google Scholar] [CrossRef] [PubMed]
[3] Stites, E.C. (2024) The Abundance of KRAS and RAS Gene Mutations in Cancer. In: Stephen, A.G. and Esposito, D., Eds., KRAS, Springer, 13-22. [Google Scholar] [CrossRef] [PubMed]
[4] Singhal, A., Li, B.T. and O’Reilly, E.M. (2024) Targeting KRAS in Cancer. Nature Medicine, 30, 969-983. [Google Scholar] [CrossRef] [PubMed]
[5] Smith, B., Sharma, A.K., Ma, R., Rigby, M., Kumari, V., Esposito, D., et al. (2023) Abstract A033: KRAS Codon 12 Oncogenic Mutations Modulate Protein Conformation within the Switch II/Helix3 Pocket. Molecular Cancer Research, 21, A033-A033. [Google Scholar] [CrossRef] 
[6] Chen, J., Zeng, Q., Wang, W., Hu, Q. and Bao, H. (2022) Q61 Mutant-Mediated Dynamics Changes of the GTP-KRAS Complex Probed by Gaussian Accelerated Molecular Dynamics and Free Energy Landscapes. RSC Advances, 12, 1742-1757. [Google Scholar] [CrossRef] [PubMed]
[7] Song, Y., Yang, X. and Yu, B. (2022) KRAS Q61H Mutation Confers Cancer Cells with Acquired Resistance to SHP2 Inhibition. Pharmaceutical Fronts, 04, e40-e42. [Google Scholar] [CrossRef] 
[8] Hong, D.S., Fakih, M.G., Strickler, J.H., Desai, J., Durm, G.A., Shapiro, G.I., et al. (2020) KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. New England Journal of Medicine, 383, 1207-1217. [Google Scholar] [CrossRef] [PubMed]
[9] Langer, C.J., Galot, R., Prenen, H., Hong, D.S., Victoria, I., Salgia, R., et al. (2024) Sotorasib Plus Panitumumab for Pre-Treated Non-Small Cell Lung Cancer with KRASG12C Mutation: A Phase 1b Study. Journal of Clinical Oncology, 42, 8559-8559. [Google Scholar] [CrossRef] 
[10] Tanaka, N. and Ebi, H. (2024) Mechanisms of Resistance to KRAS Inhibitors: Cancer Cells’ Strategic Use of Normal Cellular Mechanisms to Adapt. Cancer Science, 116, 600-612. [Google Scholar] [CrossRef] [PubMed]
[11] Jänne, P.A., Rybkin, I.I., Spira, A.I., Riely, G.J., Papadopoulos, K.P., Sabari, J.K., et al. (2020) KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Advanced/ Metastatic Non-Small-Cell Lung Cancer (NSCLC) Harboring KRAS G12C Mutation. European Journal of Cancer, 138, S1-S2. [Google Scholar] [CrossRef] 
[12] Fuchs, J., Früh, M., Papachristofilou, A., Bubendorf, L., Häuptle, P., Jost, L., et al. (2021) Resection of Isolated Brain Metastases in Non-Small Cell Lung Cancer (NSCLC) Patients—Evaluation of Outcome and Prognostic Factors: A Retrospective Multicenter Study. PLOS ONE, 16, e0253601. [Google Scholar] [CrossRef] [PubMed]
[13] Waqar, S.N., Samson, P.P., Robinson, C.G., Bradley, J., Devarakonda, S., Du, L., et al. (2018) Non-Small-Cell Lung Cancer with Brain Metastasis at Presentation. Clinical Lung Cancer, 19, e373-e379. [Google Scholar] [CrossRef] [PubMed]
[14] Sabari, J.K., Velcheti, V., Shimizu, K., Strickland, M.R., Heist, R.S., Singh, M., et al. (2022) Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. Clinical Cancer Research, 28, 3318-3328. [Google Scholar] [CrossRef] [PubMed]
[15] Heist, R.S., Koyama, T., Murciano-Goroff, Y.R., Hollebecque, A., Cassier, P.A., Han, J., et al. (2024) Pan-Tumor Activity of Olomorasib (LY3537982), a Second-Generation KRAS G12C Inhibitor (G12Ci), in Patients with KRAS G12C-Mutant Advanced Solid Tumors. Journal of Clinical Oncology, 42, 3007. [Google Scholar] [CrossRef] 
[16] Yuan, J., Hao, Y., Dai, X., Hong, J., Chen, C., Huo, Z., et al. (2025) Literature Review of Advances and Challenges in KRAS G12C Mutant Non-Small Cell Lung Cancer. Translational Lung Cancer Research, 14, 2799-2820. [Google Scholar] [CrossRef] [PubMed]
[17] Lamb, Y.N. (2024) Fulzerasib: First Approval. Drugs, 84, 1665-1671. [Google Scholar] [CrossRef] [PubMed]
[18] Zhou, Q., Meng, X., Sun, L., Huang, D., Yang, N., Yu, Y., et al. (2024) Efficacy and Safety of KRAS G12C Inhibitor IBI351 Monotherapy in Patients with Advanced NSCLC: Results from a Phase 2 Pivotal Study. Journal of Thoracic Oncology, 19, 1630-1639. [Google Scholar] [CrossRef] [PubMed]
[19] Li, Z., Dang, X., Huang, D., Jin, S., Li, W., Shi, J., et al. (2024) Garsorasib in Patients with KRASG12C-Mutated Non-Small-Cell Lung Cancer in China: An Open-Label, Multicentre, Single-Arm, Phase 2 Trial. The Lancet Respiratory Medicine, 12, 589-598. [Google Scholar] [CrossRef] [PubMed]
[20] Li, Z., Song, Z., Zhao, Y., Wang, P., Jiang, L., Gong, Y., et al. (2023) D-1553 (Garsorasib), a Potent and Selective Inhibitor of KRASG12C in Patients with NSCLC: Phase 1 Study Results. Journal of Thoracic Oncology, 18, 940-951. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, X., Allen, S., Blake, J.F., Bowcut, V., Briere, D.M., Calinisan, A., et al. (2022) Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor. Journal of Medicinal Chemistry, 65, 3123-3133. [Google Scholar] [CrossRef] [PubMed]
[22] Tanaka, Y., Tsukuda, M., Yamamoto, G., Sugiyama, E., Izumi, H., Sakai, T., et al. (2025) Abstract 7198: Preclinical Efficacy of the Combination of MEK Inhibitor Plus KRAS G12D Inhibitor for Non-Small Cell Lung Cancer with KRAS G12D. Cancer Research, 85, 7198-7198. [Google Scholar] [CrossRef] 
[23] Cregg, J., Edwards, A.V., Chang, S., Lee, B.J., Knox, J.E., Tomlinson, A.C.A., et al. (2025) Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-Selective, Noncovalent Tri-Complex Inhibitor for the Treatment of Patients with Multiple Ras-Addicted Cancers. Journal of Medicinal Chemistry, 68, 6064-6083. [Google Scholar] [CrossRef] [PubMed]
[24] Jiang, J., Jiang, L., Maldonato, B.J., Wang, Y., Holderfield, M., Aronchik, I., et al. (2024) Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in Ras-Driven Cancers. Cancer Discovery, 14, 994-1017. [Google Scholar] [CrossRef] [PubMed]
[25] Lu, J., Hu, M., Zhao, Y., Chu, T., Zhang, W., Zhou, Y., et al. (2025) Coinhibition of the MEK/RTK Pathway Has High Therapeutic Efficacy in KRAS-Mutant Non-Small Cell Lung Cancer. Signal Transduction and Targeted Therapy, 10, Article No. 299. [Google Scholar] [CrossRef] 
[26] Majem, M., Gregorc, V., Russo, G.L., Maio, M., Salvagni, S., Calderon, V.G., et al. (2025) LBA1: First-Line (1L) Fulzerasib + Cetuximab in KRAS G12Cm Advanced NSCLC: Updated Efficacy and Safety from KROCUS Study. Journal of Thoracic Oncology, 20, S1. [Google Scholar] [CrossRef] 
[27] Kazi, A., Vasiyani, H., Ghosh, D., Bandyopadhyay, D., Shah, R.D., Vudatha, V., et al. (2025) FGTI-2734 Inhibits ERK Reactivation to Overcome Sotorasib Resistance in KRAS G12C Lung Cancer. Journal of Thoracic Oncology, 20, 331-344. [Google Scholar] [CrossRef] [PubMed]
[28] Roque, K., Ruiz, R., Mas, L., Pozza, D.H., Vancini, M., Silva Júnior, J.A., et al. (2023) Update in Immunotherapy for Advanced Non-Small Cell Lung Cancer: Optimizing Treatment Sequencing and Identifying the Best Choices. Cancers, 15, Article 4547. [Google Scholar] [CrossRef] [PubMed]
[29] Wei, K., Sun, T., Feng, X., Chen, Y., Liu, Q. and Tang, H. (2025) PD-1/L1 Immune Checkpoint Inhibitors for Kras-Mutant Non-Small Cell Lung Cancer: A Multicenter Retrospective Real-World Study. BMC Cancer, 25, Article No. 444. [Google Scholar] [CrossRef] [PubMed]
[30] Eklund, E.A., Sayin, S.I., Jonsson, J.S., van Renswoude, H., Nyman, J., Hallqvist, A., et al. (2025) Monotherapy with Immune Checkpoint Blockade Improves Survival Outcomes in Kras-Mutant but Not KRAS Wild-Type Metastatic Lung Adenocarcinoma: Validation from an Extended Swedish Cohort. JTO Clinical and Research Reports, 6, Article ID: 100880. [Google Scholar] [CrossRef] 
[31] Fu, S., Ma, J., Cai, C., Tan, J., Deng, X., Shen, H., et al. (2025) Precision Immune Regulation in KRAS-Mutated Cancers: The Final Piece of the Puzzle? Journal of Experimental & Clinical Cancer Research, 44, Article No. 189. [Google Scholar] [CrossRef] [PubMed]
[32] Zhao, R., Shu, Y., Xu, W., Jiang, F., Ran, P., Pan, L., et al. (2024) The Efficacy of Immunotherapy in Non-Small Cell Lung Cancer with KRAS Mutation: A Systematic Review and Meta-Analysis. Cancer Cell International, 24, Article No. 361. [Google Scholar] [CrossRef] [PubMed]
[33] Wang, T., Chen, Z., Zhang, Y., Liu, M., Sui, H. and Tang, Q. (2025) Recent Advances in the Development and Application of Colorectal Cancer Mouse Models. Frontiers in Pharmacology, 16, Article 1553637. [Google Scholar] [CrossRef] [PubMed]
[34] Ottaiano, A., Sabbatino, F., Perri, F., Cascella, M., Sirica, R., Patrone, R., et al. (2023) KRAS p.G12C Mutation in Metastatic Colorectal Cancer: Prognostic Implications and Advancements in Targeted Therapies. Cancers, 15, Article 3579. [Google Scholar] [CrossRef] [PubMed]
[35] Fakih, M.G., Kopetz, S., Kuboki, Y., Kim, T.W., Munster, P.N., Krauss, J.C., et al. (2022) Sotorasib for Previously Treated Colorectal Cancers with KRASG12C Mutation (CodeBreaK100): A Prespecified Analysis of a Single-Arm, Phase 2 Trial. The Lancet Oncology, 23, 115-124. [Google Scholar] [CrossRef] [PubMed]
[36] Ponsioen, B., Post, J.B., Buissant des Amorie, J.R., Laskaris, D., van Ineveld, R.L., Kersten, S., et al. (2021) Quantifying Single-Cell ERK Dynamics in Colorectal Cancer Organoids Reveals EGFR as an Amplifier of Oncogenic MAPK Pathway Signalling. Nature Cell Biology, 23, 377-390. [Google Scholar] [CrossRef] [PubMed]
[37] Pietrantonio, F., Salvatore, L., Esaki, T., Modest, D.P., Lopez-Bravo, D.P., Taieb, J., et al. (2025) Overall Survival Analysis of the Phase III Codebreak 300 Study of Sotorasib Plus Panitumumab versus Investigator’s Choice in Chemorefractory KRAS G12C Colorectal Cancer. Journal of Clinical Oncology, 43, 2147-2154. [Google Scholar] [CrossRef] [PubMed]
[38] Li, F., Lin, Y., Li, R., Shen, X., Xiang, M., Xiong, G., et al. (2023) Molecular Targeted Therapy for Metastatic Colorectal Cancer: Current and Evolving Approaches. Frontiers in Pharmacology, 14, Article 1165666. [Google Scholar] [CrossRef] [PubMed]
[39] Ruan, D., Wu, H., Xu, Y., Munster, P.N., Deng, Y., Richardson, G., et al. (2025) Garsorasib, a KRAS G12C Inhibitor, with or without Cetuximab, an EGFR Antibody, in Colorectal Cancer Cohorts of a Phase II Trial in Advanced Solid Tumors with KRAS G12C Mutation. Signal Transduction and Targeted Therapy, 10, Article No. 189. [Google Scholar] [CrossRef] [PubMed]
[40] Ma, X., Sloman, D.L., Duggal, R., Anderson, K.D., Ballard, J.E., Bharathan, I., et al. (2024) Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRASG12C Inhibitor. Journal of Medicinal Chemistry, 67, 11024-11052. [Google Scholar] [CrossRef] [PubMed]
[41] Lugowska, I.A., Simonelli, M., Xue, J., Sacher, A.G., Stathis, A., Dziadziuszko, R., et al. (2025) The KRAS G12C Inhibitor MK-1084 for KRAS G12C-Mutated Advanced Colorectal Cancer (CRC): Results from Kandlelit-001. Journal of Clinical Oncology, 43, 3508-3508. [Google Scholar] [CrossRef] 
[42] Pei, B., Peng, S., Chen, W., Lai, L. and Zhou, F. (2025) Combining Cetuximab and Immunotherapy for Treating MSS/pMMR Colorectal Cancer: Current Evidence and Challenges. Technology in Cancer Research & Treatment, 24. [Google Scholar] [CrossRef] [PubMed]
[43] Li, Y., Du, Y., Xue, C., Wu, P., Du, N., Zhu, G., et al. (2022) Efficacy and Safety of Anti-PD-1/PD-L1 Therapy in the Treatment of Advanced Colorectal Cancer: A Meta-Analysis. BMC Gastroenterology, 22, Article No. 431. [Google Scholar] [CrossRef] [PubMed]
[44] Tanegashima, T., Shiota, M., Toyosaki, K., Funakoshi, K. and Eto, M. (2025) Biology and Evolving Management of Resectable dMMR/MSI-H Cancers: Current Status and Future Perspectives. Cancer Immunology, Immunotherapy, 74, Article No. 364. [Google Scholar] [CrossRef] 
[45] Motta, R., Cabezas-Camarero, S., Torres-Mattos, C., et al. (2021) Personalizing First-Line Treatment in Advanced Colorectal Cancer: Present Status and Future Perspectives. Journal of Clinical and Translational Research, 7, 771-785.
[46] Wookey, V. and Grothey, A. (2021) Update on the Role of Pembrolizumab in Patients with Unresectable or Metastatic Colorectal Cancer. Therapeutic Advances in Gastroenterology, 14. [Google Scholar] [CrossRef] [PubMed]
[47] André, T., Lonardi, S., Wong, K.Y.M., Lenz, H., Gelsomino, F., Aglietta, M., et al. (2022) Nivolumab Plus Low-Dose Ipilimumab in Previously Treated Patients with Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: 4-Year Follow-Up from Checkmate 142. Annals of Oncology, 33, 1052-1060. [Google Scholar] [CrossRef] [PubMed]
[48] Zhou, Y., Kuang, Y., Wang, C., Yu, Y., Pan, L. and Hu, X. (2024) Impact of KRAS Mutation on the Tumor Microenvironment in Colorectal Cancer. International Journal of Biological Sciences, 20, 1947-1964. [Google Scholar] [CrossRef] [PubMed]
[49] Cataldi, C., Karaoğlan, B.B., Liotta, E. and De Dosso, S. (2026) Decoding Immunotherapy Response in Colorectal Cancer: Translational Insights Beyond MSI. Cancers, 18, Article 852. [Google Scholar] [CrossRef] 
[50] Stickler, S., Rath, B. and Hamilton, G. (2024) Targeting KRAS in Pancreatic Cancer. Oncology Research, 32, 799-805. [Google Scholar] [CrossRef] [PubMed]
[51] Muller, M. and Tougeron, D. (2023) KRAS G12C Inhibitors: Also a New Promising New Targeted Therapy in Advanced Pancreatic Adenocarcinoma? Translational Cancer Research, 12, 3227-3232. [Google Scholar] [CrossRef] [PubMed]
[52] Hallin, J., Bowcut, V., Calinisan, A., Briere, D.M., Hargis, L., Engstrom, L.D., et al. (2022) Anti-Tumor Efficacy of a Potent and Selective Non-Covalent KRASG12D Inhibitor. Nature Medicine, 28, 2171-2182. [Google Scholar] [CrossRef] [PubMed]
[53] Spira, A.I., Papadopoulos, K.P., Kim, D.W., Parikh, A.R., Barve, M.A., Powderly, J.D., et al. (2025) 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.. Journal of Clinical Oncology, 43, 724-724. [Google Scholar] [CrossRef] 
[54] Ai, X., Zhou, A., Wu, L., Song, Z., Li, Z., Wu, H., et al. (2025) A First-In-Human Phase I/II Study of GFH375, a Highly Selective and Potent Oral KRAS G12D Inhibitor in Patients with KRAS G12D Mutant Advanced Solid Tumors. Journal of Clinical Oncology, 43, 3013-3013. [Google Scholar] [CrossRef] 
[55] Fu, S., Shen, L., Lu, S., Sommerhalder, D., Liu, T., Spira, A., et al. (2025) The First-In-Human Phase 1/2 Study of TSN1611, a Highly Selective KRAS G12D Inhibitor, in Patients with Advanced Solid Tumors. Journal of Clinical Oncology, 43, 3083-3083. [Google Scholar] [CrossRef] 
[56] Kazi, A., Ranjan, A., Kumar, V.M., Agianian, B., Chavez, M.G., Vudatha, V., et al. (2025) Abstract 4326: KRB-456: A Novel KRAS G12D Switch-I/II Allosteric Pocket Binder That Thwarts Pancreatic Cancer Patient-Derived Tumors. Cancer Research, 85, 4326-4326. [Google Scholar] [CrossRef] 
[57] Bandi, D.S.R., Ganji, P.N., Sarvesh, S., Maxuitenko, Y., Foote, J.B., Keeton, A.B., et al. (2024) Abstract 5915: ADT-1004: A Promising Pan-Ras Inhibitor for Targeting KRAS Mutations in Pancreatic Ductal Adenocarcinoma. Cancer Research, 84, 5915-5915. [Google Scholar] [CrossRef] 
[58] Atalay, P., Ture, A., Kahraman, N., Fokt, I., Priebe, W., Buyukbingol, E., et al. (2025) Abstract 6390: Identification of Novel Pan-KRAS Mutation Inhibitor Shows Significant Efficacy in Pancreatic Cancer with No Toxicity, Offering Hope Beyond Current Therapies. Cancer Research, 85, 6390-6390. [Google Scholar] [CrossRef] 
[59] Tushoski-Alemán, G.W., Crespin, A.J., Oguejiofor, C.J., McKean, J.A., Herremans, K.M., George, T.J., et al. (2024) Abstract 7223: A Triplet Therapeutic Strategy Targeting MEK, BCL-XL, and EGFR, for Kras-Mutant Pancreatic Ductal Adenocarcinoma. Cancer Research, 84, 7223-7223. [Google Scholar] [CrossRef] 
[60] Bargenquast, T., Wesley, C., Don, J., Zhang, G., Halder, T.G., Ng, S., et al. (2025) Abstract 4706: Evaluating the Efficacy of RAS(ON) Inhibitor RMC-6236 Combined with Chemotherapy and Other Targeted Therapies in 3D Models Involving Patients with KRAS-Mutated Pancreatic Cancer. Cancer Research, 85, 4706-4706. [Google Scholar] [CrossRef] 
[61] Hao, M., Zhang, T., Dong, D., Zhou, X. and Gao, H. (2025) Enhancing KRAS G12D Inhibitor Sensitivity in Pancreatic Cancer through SHP2/PI3K Pathway. Medical Oncology, 42, Article No. 139. [Google Scholar] [CrossRef] [PubMed]
[62] Christenson, E.S., Yu, R., Gai, J., Wang, H., Lei, M. and Zheng, L. (2024) The Impact of KRAS Mutations on the Clinical Outcome and Immune Response Following Immunotherapy for Pancreatic Cancer. Annals of Pancreatic Cancer, 7, Article 6. [Google Scholar] [CrossRef] [PubMed]
[63] Chick, R.C. and Pawlik, T.M. (2024) Updates in Immunotherapy for Pancreatic Cancer. Journal of Clinical Medicine, 13, Article 6419. [Google Scholar] [CrossRef] [PubMed]
[64] Sethna, Z., Guasp, P., Reiche, C., Milighetti, M., Ceglia, N., Patterson, E., et al. (2025) RNA Neoantigen Vaccines Prime Long-Lived CD8+ T Cells in Pancreatic Cancer. Nature, 639, 1042-1051. [Google Scholar] [CrossRef] [PubMed]
[65] Wainberg, Z.A., Weekes, C.D., Furqan, M., Kasi, P.M., Devoe, C.E., Leal, A.D., et al. (2025) Lymph Node-Targeted, mKRAS-Specific Amphiphile Vaccine in Pancreatic and Colorectal Cancer: Phase 1 AMPLIFY-201 Trial Final Results. Nature Medicine, 31, 3648-3653. [Google Scholar] [CrossRef] [PubMed]
[66] Thatikonda, V., Lyu, H., Jurado, S., Kostyrko, K., Bristow, C.A., Albrecht, C., et al. (2024) Co-Targeting SOS1 Enhances the Antitumor Effects of KRASG12C Inhibitors by Addressing Intrinsic and Acquired Resistance. Nature Cancer, 5, 1352-1370. [Google Scholar] [CrossRef] [PubMed]
[67] Chidambaram, K., Rekha, A., Goyal, A. and Rana, M. (2025) Targeting KRAS-G12C in Lung Cancer: The Emerging Role of PROTACs in Overcoming Resistance. Pathology—Research and Practice, 270, Article ID: 155954. [Google Scholar] [CrossRef] [PubMed]
[68] Kargbo, R.B. (2025) Targeting KRAS G12D Mutations: Advances in Small Molecule Inhibitors and PROTAC Technology. ACS Medicinal Chemistry Letters, 16, 746-747. [Google Scholar] [CrossRef] [PubMed]
[69] Piech, S., Brüschweiler, S., Westphalen, J., Siess, K.M., García Murias, J., Konrat, R., et al. (2024) Identification and Characterization of Novel Small-Molecule Enhancers of the CUL3LZTR1 E3 Ligase KRAS Complex. ACS Chemical Biology, 19, 1942-1952. [Google Scholar] [CrossRef] [PubMed]
[70] Cregg, J., Pota, K., Tomlinson, A.C.A., Yano, J., Marquez, A., Liu, Y., et al. (2025) Discovery of Elironrasib (RMC-6291), a Potent and Orally Bioavailable, RAS(ON) G12C-Selective, Covalent Tricomplex Inhibitor for the Treatment of Patients with RAS G12C-Addicted Cancers. Journal of Medicinal Chemistry, 68, 6041-6063. [Google Scholar] [CrossRef] [PubMed]
[71] Conn, B.P., Dietze, J.L., Yee, C.J., Hallisey, M.M., Ortiz-Caraveo, I., van Buuren, M.M., et al. (2025) Generation of T Cell Responses against Broad KRAS Hotspot Neoantigens for Cell Therapy or TCR Discovery. Cell Reports Methods, 5, Article ID: 101049. [Google Scholar] [CrossRef] [PubMed]

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