Enhancing KRAS G12D inhibitor sensitivity in pancreatic cancer through SHP2/PI3K pathway

Wood LD, Canto MI, Jaffee EM, et al. Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment. Gastroenterology. 2022;163(2):386–402. https://doi.org/10.1053/j.gastro.2022.03.056.

Article  PubMed  Google Scholar 

Chibaya L, DeMarco K, Lusi C, et al. Nanoparticle delivery of innate immune agonists combined with senescence-inducing agents promotes T cell control of pancreatic cancer. Sci Transl Med. 2024;16(762):eadj9366. https://doi.org/10.1126/scitrans-lmed.adj9366.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang N, Fan ZY, Sun SY, et al. Discovery of highly potent and selective KRASG12C degraders by VHL-recruiting PROTACs for the treatment of tumors with KRASG12C-Mutation. Eur J Med Chem. 2023;5(261): 115857. https://doi.org/10.1016/j.ejmech.2023.115857.

Article  CAS  Google Scholar 

Li J, Wang X, Huang Y, et al. Preliminary activity and safety results of KRAS G12C inhibitor glecirasib (JAB-21822) in patients with pancreatic cancer and other solid tumors. J Clin Oncol. 2024;42(3):604.

CAS  Google Scholar 

Yang J, Xu R, Wang C, et al. Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review. Cancer Commun (Lond). 2021;41(12):1257–74. https://doi.org/10.1002/cac2.12204.

Article  CAS  PubMed  Google Scholar 

Timar J, Kashofer K. Molecular epidemiology and diagnostics of KRAS mutations in human cancer. Cancer Metastasis Rev. 2020;39(4):1029–38. https://doi.org/10.1007/s10555-020-09915-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, et al. Pancreatic cancer: advances and challenges. Cell. 2023;186(8):1729–54. https://doi.org/10.1016/j.cell.2023.02.014.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. https://doi.org/10.3322/caac.21763.

Article  PubMed  Google Scholar 

Klomp JA, Klomp JE, Stalnecker CA, et al. Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers. Science. 2024;384(6700):eadk0775. https://doi.org/10.1126/science.adk0775.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang YF, Xu LS, Ling LJ, et al. Unraveling the CDK9/PP2A/ERK network in transcriptional pause release and complement activation in KRAS-mutant cancers. Adv Sci (Weinh). 2024;11(41): e2404926.

PubMed  Google Scholar 

Yang J, Wang QL, Wang GN, et al. A pan-KRAS degrader for the treatment of KRAS-mutant cancers. Cell Discov. 2024;10(1):70. https://doi.org/10.1038/s41421-024-00699-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hallin J, Bowcut V, Calinisan A, et al. Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor. Nat Med. 2022;28(10):2171–82. https://doi.org/10.1038/s41591-022-02007-7.

Article  CAS  PubMed  Google Scholar 

Kemp SB, Cheng N, Markosyan N, et al. Efficacy of a small-molecule inhibitor of KrasG12D in immunocompetent models of pancreatic cancer. Cancer Discov. 2023;13(2):298–311. https://doi.org/10.1158/2159-8290.

Article  CAS  PubMed  Google Scholar 

Tinsley SL, Chianis ERD, Shelley RA, et al. KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56alpha to initiate pancreatic cancer development. Oncogene. 2024. https://doi.org/10.1038/s41388-024-03196-w.

Article  PubMed  Google Scholar 

McDaid WJ, Wilson L, Adderley H, et al. The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer. Mol Cancer. 2024;23(1):253. https://doi.org/10.1186/s12943-024-02157-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ullah R, Yin Q, Snell AH, et al. RAF-MEK-ERK pathway in cancer evolution and treatment. Semin Cancer Biol. 2022;85:123–54. https://doi.org/10.1016/j.semcancer.2021.05.010.

Article  CAS  PubMed  Google Scholar 

Li Q, Li Z, Luo T, et al. Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol Biomed. 2022;3(1):47. https://doi.org/10.1186/s43556-022-00110-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hamarsheh S, Groß O, Brummer T, et al. Immune modulatory effects of oncogenic KRAS in cancer. Nat Commun. 2020;11(1):5439. https://doi.org/10.1038/s41467-020-19288-6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lanman BA, Allen JR, Allen JG, et al. Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors. J Med Chem. 2020;63(1):52–65. https://doi.org/10.1021/acs.jmedchem.9b01180.

Article  CAS  PubMed  Google Scholar 

Dhillon S. Adagrasib: first approval. Drugs. 2023;83(3):275–85. https://doi.org/10.1007/s40265-023-01839-y.

Article  CAS  PubMed  Google Scholar 

Wang X, Allen S, Blake JF, et al. Identification of MRTX1133, a noncovalent, potent, and selective KRASG12D inhibitor. J Med Chem. 2022;65(4):3123–33. https://doi.org/10.1021/acs.jmedchem.1c01688.

Article  CAS  PubMed  Google Scholar 

Reck M, Carbone DP, Garassino M, et al. Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches. Ann Oncol. 2021;32(9):1101–10. https://doi.org/10.1016/j.annonc.2021.06.001.

Article  CAS  PubMed  Google Scholar 

Ryan MB, Coker O, Sorokin A, et al. KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy. Cell Rep. 2022;39(12): 110993. https://doi.org/10.1016/j.celrep.2022.110993.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Canon J, Rex K, Saiki AY, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019;575(7781):217–23. https://doi.org/10.1038/s41586-019-1694-1.

Article  CAS  PubMed  Google Scholar 

Prahallad A, Weiss A, Voshol H, et al. CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer. Cancer Res. 2023;83(24):4130–41. https://doi.org/10.1158/0008-5472.

Article  PubMed  PubMed Central  Google Scholar 

Buck SA, Koolen SL, Mathijssen RH, de Wit R, van Soest RJ. Cross-resistance and drug sequence in prostate cancer. Drug Resist Updat. 2021;56:100761. https://doi.org/10.1016/j.drup.2021.100761.

Article  CAS  PubMed  Google Scholar 

Amodio V, Yaeger R, Arcella P, et al. EGFR Blockade reverts resistance to KRASG12C inhibition in colorectal cancer. Cancer Discov. 2020;10(8):1129–39. https://doi.org/10.1158/2159-8290.CD-20-0187.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Misale S, Fatherree JP, Cortez E, et al. KRAS G12C NSCLC models are sensitive to direct targeting of KRAS in combination with PI3K inhibition. Clin Cancer Res. 2019;25(2):796–807. https://doi.org/10.1158/1078-0432.CCR-18-0368.

Article  CAS  PubMed  Google Scholar 

Song Y, Zhao M, Zhang H, et al. Double-edged roles of protein tyrosine phosphatase SHP2 in cancer and its inhibitors in clinical trials. Pharmacol Ther. 2022;230: 107966.

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