The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer

Wang YC, Morrison G, Gillihan R, Guo J, Ward RM, Fu X, et al. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers-role of estrogen receptor and HER2 reactivation. Breast Cancer Res. 2011;13:R121.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Voigtlaender M, Schneider-Merck T, Trepel M. Lapatinib. Recent Results Cancer Res. 2018;211:19–44.

Article  CAS  PubMed  Google Scholar 

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet (Lond, Engl). 2010;376:687–97.

Article  CAS  Google Scholar 

Arienti C, Zanoni M, Pignatta S, Del Rio A, Carloni S, Tebaldi M, et al. Preclinical evidence of multiple mechanisms underlying trastuzumab resistance in gastric cancer. Oncotarget. 2016;7:18424–39.

Article  PubMed  PubMed Central  Google Scholar 

Garrett JT, Olivares MG, Rinehart C, Granja-Ingram ND, Sanchez V, Chakrabarty A, et al. Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Proc Natl Acad Sci USA. 2011;108:5021–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382:2419–30.

Article  CAS  PubMed  Google Scholar 

Peng Z, Liu T, Wei J, Wang A, He Y, Yang L, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study. Cancer Commun. 2021;41:1173–82.

Article  Google Scholar 

Zhang Y, Qiu MZ, Wang JF, Zhang YQ, Shen A, Yuan XL, et al. Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma. Cell Rep Med. 2022;3:100814.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi J, Gao W, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 2017;42:245–54.

Article  CAS  PubMed  Google Scholar 

Kovacs SB, Miao EA. Gasdermins: effectors of pyroptosis. Trends Cell Biol. 2017;27:673–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Broz P, Pelegrin P, Shao F. The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2020;20:143–57.

Article  CAS  PubMed  Google Scholar 

Wang Y, Gao W, Shi X, Ding J, Liu W, He H, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547:99–103.

Article  CAS  PubMed  Google Scholar 

Lu H, Zhang S, Wu J, Chen M, Cai MC, Fu Y, et al. Molecular targeted therapies elicit concurrent apoptotic and GSDME-dependent pyroptotic tumor cell death. Clin Cancer Res. 2018;24:6066–77.

Article  CAS  PubMed  Google Scholar 

Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, et al. Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature. 2020;579:415–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Peng Z, Wang P, Song W, Yao Q, Li Y, Liu L, et al. GSDME enhances cisplatin sensitivity to regress non-small cell lung carcinoma by mediating pyroptosis to trigger antitumor immunocyte infiltration. Signal Transduct Target Ther. 2020;5:159.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Y, Yin B, Li D, Wang G, Han X, Sun X. GSDME mediates caspase-3-dependent pyroptosis in gastric cancer. Biochem Biophys Res Commun. 2018;495:1418–25.

Article  CAS  PubMed  Google Scholar 

Yin J, Che G, Wang W, Chen S, Liu J. Investigating the prognostic significance of pyroptosis-related genes in gastric cancer and their impact on cells’ biological functions. Front Oncol. 2022;12:861284.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jia C, Zhang Z, Tang J, Cai MC, Zang J, Shi K, et al. Epithelial-mesenchymal transition induces GSDME transcriptional activation for inflammatory pyroptosis. Front Cell Dev Biol. 2021;9:781365.

Article  PubMed  PubMed Central  Google Scholar 

Xu L, Shi F, Wu Y, Yao S, Wang Y, Jiang X, et al. Gasdermin E regulates the stability and activation of EGFR in human non-small cell lung cancer cells. Cell Commun Signal. 2023;21:83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin J, Xiong Y, Cen B. Bcl-2 and Bcl-xL mediate resistance to receptor tyrosine kinase-targeted therapy in lung and gastric cancer. Anticancer Drugs. 2017;28:1141–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang J, Yang D, Luo Q, Qiu M, Zhang L, Li B, et al. APG-1252-12A induces mitochondria-dependent apoptosis through inhibiting the antiapoptotic proteins Bcl-2/Bcl-xl in HL-60 cells. Int J Oncol. 2017;51:563–72.

Article  CAS  PubMed  Google Scholar 

Luo F, Lu FT, Qiu MZ, Zhou T, Ma WJ, Luo M, et al. Gemcitabine and APG-1252, a novel small molecule inhibitor of BCL-2/BCL-XL, display a synergistic antitumor effect in nasopharyngeal carcinoma through the JAK-2/STAT3/MCL-1 signaling pathway. Cell Death Dis. 2021;12:772.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yi H, Qiu MZ, Yuan L, Luo Q, Pan W, Zhou S, et al. Bcl-2/Bcl-xl inhibitor APG-1252-M1 is a promising therapeutic strategy for gastric carcinoma. Cancer Med. 2020;9:4197–206.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qian L, Vallega KA, Yao W, Wang D, Zhai Y, He X, et al. Therapeutic potential of the novel Bcl-2/Bcl-X(L) dual inhibitor, APG1252, alone or in combination against non-small cell lung cancer. Mol Carcinog. 2022;61:1031–42.

Article  CAS  PubMed  Google Scholar 

Hu L, Chen M, Chen X, Zhao C, Fang Z, Wang H, et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death Dis. 2020;11:281.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ren J, Tao Y, Peng M, Xiao Q, Jing Y, Huang J, et al. Targeted activation of GPER enhances the efficacy of venetoclax by boosting leukemic pyroptosis and CD8+ T cell immune function in acute myeloid leukemia. Cell Death Dis. 2022;13:915.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barok M, Tanner M, Koninki K, Isola J. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett. 2011;306:171–9.

Article  CAS  PubMed  Google Scholar 

Park J, Choi Y, Ko YS, Kim Y, Pyo JS, Jang BG, et al. FOXO1 suppression is a determinant of acquired lapatinib-resistance in HER2-positive gastric cancer cells through MET upregulation. Cancer Res Treat. 2018;50:239–54.

Article  CAS  PubMed  Google Scholar 

Liu J, Lichtenberg T, Hoadley KA, Poisson LM, Lazar AJ, Cherniack AD, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell. 2018;173:400–16.e411.

Article  CAS  PubMed 

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