REFERENCES
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
2. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965;64:31-49.
3. Fléjou JF. WHO Classification of digestive tumors: the fourth edition. Ann Pathol 2011;31:S27-31.
4. Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202-9.
5. Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med 2015;21:449-56.
7. Jim MA, Pinheiro PS, Carreira H, Espey DK, Wiggins CL, Weir HK. Stomach cancer survival in the United States by race and stage (2001-2009): findings from the CONCORD-2 study. Cancer 2017;123 Suppl 24:4994-5013.
8. MacDonald JS, Schein PS, Woolley PV, et al. 5-Fluorouracil, doxorubicin, and mitomycin (FAM) combination chemotherapy for advanced gastric cancer. Ann Intern Med 1980;93:533-6.
9. Wils JA, Klein HO, Wagener DJ, et al. Sequential high-dose methotrexate and fluorouracil combined with doxorubicin-a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol 1991;9:827-31.
10. Webb A, Cunningham D, Scarffe JH, et al. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 1997;15:261-7.
11. Cutsem E, Moiseyenko VM, Tjulandin S, et al; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24:4991-7.
12. Cunningham D, Starling N, Rao S, et al. Upper gastrointestinal clinical studies group of the national cancer research institute of the united kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36-46.
13. Kang YK, Kang WK, Shin DB, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009;20:666-73.
14. Shah MA, Janjigian YY, Stoller R, et al. Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the US gastric cancer consortium. J Clin Oncol 2015;33:3874-9.
15. Koizumi W, Kim YH, Fujii M, et al. JACCRO and KCSG Study Group. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol 2014;140:319-28.
16. Guimbaud R, Louvet C, Ries P, et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol 2014;32:3520-6.
17. Li K, Zhang A, Li X, Zhang H, Zhao L. Advances in clinical immunotherapy for gastric cancer. Biochim Biophys Acta Rev Cancer 2021;1876:188615.
18. Hsu A, Raufi AG. Advances in Systemic Therapy for gastric cancer. Gastrointest Endosc Clin N Am 2021;31:607-23.
19. Bang Y, Van Cutsem E, Feyereislova 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 2010;376:687-97.
20. Shitara K, Bang YJ, Iwasa S, et al. DESTINY-Gastric01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020;382:2419-30.
21. Satoh T, Xu RH, Chung HC, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN-a randomized, phase III study. J Clin Oncol 2014;32:2039-49.
22. Hecht JR, Bang YJ, Qin SK, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol 2016;34:443-51.
23. Rugo HS, Im SA, Cardoso F, et al. SOPHIA Study Group. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol 2021;7:573-84.
24. Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 2011;29:3968-76.
25. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014;383:31-9.
26. Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014;15:1224-35.
27. Li J, Qin S, Xu J, et al. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol 2016;34:1448-54.
28. Pavlakis N, Sjoquist KM, Martin AJ, et al. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): a multinational placebo-controlled phase II trial. J Clin Oncol 2016;34:2728-35.
29. Lordick F, Kang Y, Chung H, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14:490-9.
30. Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol 2013;14:481-9.
31. Catenacci DVT, Rasco D, Lee J, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol 2020;38:2418-26.
32. Ohtsu A, Ajani JA, Bai YX, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol 2013;31:3935-43.
33. Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res 2008;14:7624-34.
34. Kang Y, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:2461-71.
35. Shitara K, Van Cutsem E, Bang YJ, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial. JAMA Oncol 2020;6:1571-80.
36. Shitara K, Özgüroğlu M, Bang Y, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 2018;392:123-33.
37. Kelly RJ, Lee J, Bang YJ, et al. Safety and Efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma. Clin Cancer Res 2020;26:846-54.
38. Bang YJ, Ruiz EY, Van Cutsem E, et al. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol 2018;29:2052-60.
39. Bang YJ, Cho JY, Kim YH, et al. Efficacy of sequential ipilimumab monotherapy versus best supportive care for unresectable locally advanced/metastatic gastric or gastroesophageal junction cancer. Clin Cancer Res 2017;23:5671-8.
40. Marin JJG, Perez-Silva L, Macias RIR, et al. Molecular bases of mechanisms accounting for drug resistance in gastric adenocarcinoma. Cancers (Basel) 2020;12:2116.
41. Pützer BM, Solanki M, Herchenröder O. Advances in cancer stem cell targeting: how to strike the evil at its root. Adv Drug Deliv Rev 2017;120:89-107.
42. Valent P, Bonnet D, De Maria R, et al. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer 2012;12:767-75.
44. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396-401.
45. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003;100:3983-8.
46. Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007;104:973-8.
47. Bussolati B, Dekel B, Azzarone B, Camussi G. Human renal cancer stem cells. Cancer Lett 2013;338:141-6.
48. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106-10.
49. Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445:111-5.
50. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007;104:10158-63.
51. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007;67:1030-7.
52. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007;1:313-23.
53. Ma S, Chan KW, Hu L, et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 2007;132:2542-56.
54. Lundin A, Driscoll B. Lung cancer stem cells: progress and prospects. Cancer Lett 2013;338:89-93.
55. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005;65:10946-51.
56. Fang D, Nguyen TK, Leishear K, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 2005;65:9328-37.
57. Yang L, Shi P, Zhao G, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther 2020;5:8.
58. Xiao W, Gao Z, Duan Y, Yuan W, Ke Y. Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma. J Exp Clin Cancer Res 2017;36:41.
59. Mohammed MK, Shao C, Wang J, et al. Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance. Genes Dis 2016;3:11-40.
60. Bekaii-Saab T, El-Rayes B. Identifying and targeting cancer stem cells in the treatment of gastric cancer. Cancer 2017;123:1303-12.
62. Nunes T, Hamdan D, Leboeuf C, et al. Targeting cancer stem cells to overcome chemoresistance. Int J Mol Sci 2018;19:4036.
63. Brungs D, Aghmesheh M, Vine KL, Becker TM, Carolan MG, Ranson M. Gastric cancer stem cells: evidence, potential markers, and clinical implications. J Gastroenterol 2016;51:313-26.
64. Li Y, Wang Z, Ajani JA, Song S. Drug resistance and cancer stem cells. Cell Commun Signal 2021;19:19.
65. Takaishi S, Okumura T, Tu S, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 2009;27:1006-20.
66. Qiao XT, Gumucio DL. Current molecular markers for gastric progenitor cells and gastric cancer stem cells. J Gastroenterol 2011;46:855-65.
67. Fu L, Bu L, Yasuda T, et al. Gastric cancer stem cells: current insights into the immune microenvironment and therapeutic targets. Biomedicines 2020;8:7.
68. Ray K. Stem cells: Settling the stomach - tracing gastric stem cells. Nat Rev Gastroenterol Hepatol 2016;13:626.
70. Toledo-Guzmán ME, Hernández MI, Gómez-Gallegos ÁA, Ortiz-Sánchez E. ALDH as a stem cell marker in solid tumors. Curr Stem Cell Res Ther 2019;14:375-88.
71. Zhi QM, Chen XH, Ji J, et al. Salinomycin can effectively kill ALDH(high) stem-like cells on gastric cancer. Biomed Pharmacother 2011;65:509-15.
72. Cojoc M, Mäbert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol 2015;31:16-27.
73. Wang B, Chen Q, Cao Y, et al. LGR5 is a gastric cancer stem cell marker associated with stemness and the EMT SIgnature genes NANOG, NANOGP8, PRRX1, TWIST1, and BMI1. PLoS One 2016;11:e0168904.
74. Zhang L, Guo X, Zhang D, et al. Upregulated miR-132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway. Mol Carcinog 2017;56:2022-34.
75. Xiong J, Wang S, Chen T, et al. Verteporfin blocks Clusterin which is required for survival of gastric cancer stem cell by modulating HSP90 function. Int J Biol Sci 2019;15:312-24.
76. Ukai S, Honma R, Sakamoto N, et al. Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell. Oncogene 2020;39:7265-78.
77. Zhu Z, Xu J, Li L, et al. Effect of gastric cancer stem cell on gastric cancer invasion, migration and angiogenesis. Int J Med Sci 2020;17:2040-51.
78. Shimoda M, Ota M, Okada Y. Isolation of cancer stem cells by side population method. In: Papaccio G, Desiderio V, editors. Cancer stem cells. New York: Springer; 2018. pp. 49-59.
80. Chen W, Zhang X, Chu C, et al. Identification of CD44+ cancer stem cells in human gastric cancer. Hepatogastroenterology 2013;60:949-54.
81. Nishikawa S, Konno M, Hamabe A, et al. Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy. Int J Oncol 2013;42:1437-42.
82. Ishigami S, Ueno S, Arigami T, et al. Prognostic impact of CD133 expression in gastric carcinoma. Anticancer Res 2010;30:2453-2457. [PMID: 20651407].
83. Wang T, Ong CW, Shi J, et al. Sequential expression of putative stem cell markers in gastric carcinogenesis. Br J Cancer 2011;105:658-65.
84. Wattanawongdon W, Bathpho TS, Tongtawee T. Co-expression of LGR5 and CD133 cancer stem cell predicts a poor prognosis in patients with gastric cancer. Turk J Gastroenterol 2021;32:261-8.
85. Katoh M. Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers. Clin Sci (Lond) 2019;133:953-70.
86. Garcia-Mayea Y, Mir C, Masson F, Paciucci R, LLeonart ME. Insights into new mechanisms and models of cancer stem cell multidrug resistance. Semin Cancer Biol 2020;60:166-80.
87. Talukdar S, Bhoopathi P, Emdad L, Das S, Sarkar D, Fisher PB. Dormancy and cancer stem cells: an enigma for cancer therapeutic targeting. Cancer stem cells. Elsevier; 2019. pp. 43-84.
88. Chen K, Zhang C, Ling S, Wei R, Wang J, Xu X. The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance. Cell Death Dis 2021;12:835.
90. Takeishi S, Nakayama KI. To wake up cancer stem cells, or to let them sleep, that is the question. Cancer Sci 2016;107:875-81.
91. Xu ZY, Tang JN, Xie HX, et al. 5-Fluorouracil chemotherapy of gastric cancer generates residual cells with properties of cancer stem cells. Int J Biol Sci 2015;11:284-94.
92. Jiang YX, Yang SW, Li PA, et al. The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms. Oncogene 2017;36:1256-64.
93. Muley H, Fadó R, Rodríguez-Rodríguez R, Casals N. Drug uptake-based chemoresistance in breast cancer treatment. Biochem Pharmacol 2020;177:113959.
94. Zhang L, Guo X, Zhang L, et al. SLC34A2 regulates miR-25-Gsk3β signaling pathway to affect tumor progression in gastric cancer stem cell-like cells. Mol Carcinog 2018;57:440-50.
95. Zhang JX, Xu Y, Gao Y, et al. Decreased expression of miR-939 contributes to chemoresistance and metastasis of gastric cancer via dysregulation of SLC34A2 and Raf/MEK/ERK pathway. Mol Cancer 2017;16:18.
96. Wang JQ, Wu ZX, Yang Y, et al. ATP-binding cassette (ABC) transporters in cancer: a review of recent updates. J Evid Based Med 2021;14:232-56.
97. Li W, Zhang H, Assaraf YG, et al. Overcoming ABC transporter-mediated multidrug resistance: molecular mechanisms and novel therapeutic drug strategies. Drug Resist Updat 2016;27:14-29.
98. Gottesman MM, Pastan IH. The role of multidrug resistance efflux pumps in cancer: revisiting a JNCI publication exploring expression of the MDR1 (P-glycoprotein) gene. J Natl Cancer Inst 2015;107:djv222.
99. Duan H, Liu Y, Gao Z, Huang W. Recent advances in drug delivery systems for targeting cancer stem cells. Acta Pharm Sin B 2021;11:55-70.
100. Kim JK, Jeon HY, Kim H. The molecular mechanisms underlying the therapeutic resistance of cancer stem cells. Arch Pharm Res 2015;38:389-401.
101. Moitra K, Lou H, Dean M. Multidrug efflux pumps and cancer stem cells: insights into multidrug resistance and therapeutic development. Clin Pharmacol Ther 2011;89:491-502.
102. Pasello M, Giudice AM, Scotlandi K. The ABC subfamily A transporters: multifaceted players with incipient potentialities in cancer. Semin Cancer Biol 2020;60:57-71.
103. Xu M, Gong A, Yang H, et al. Sonic hedgehog-glioma associated oncogene homolog 1 signaling enhances drug resistance in CD44(+)/Musashi-1(+) gastric cancer stem cells. Cancer Lett 2015;369:124-33.
104. Huang W, Wan C, Luo Q, Huang Z, Luo Q. Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer. Int J Mol Sci 2014;15:3432-43.
105. Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006;366:2-16.
106. Martinelli E, Morgillo F, Troiani T, Ciardiello F. Cancer resistance to therapies against the EGFR-RAS-RAF pathway: the role of MEK. Cancer Treat Rev 2017;53:61-9.
107. Jo JH, Park SB, Park S, et al. Novel gastric cancer stem cell-related marker LINGO2 is associated with cancer cell phenotype and patient outcome. Int J Mol Sci 2019;20:555.
108. Lee SD, Yu D, Lee DY, Shin HS, Jo JH, Lee YC. Upregulated microRNA-193a-3p is responsible for cisplatin resistance in CD44(+) gastric cancer cells. Cancer Sci 2019;110:662-73.
109. Zhu M, Zhou X, Du Y, et al. miR-20a induces cisplatin resistance of a human gastric cancer cell line via targeting CYLD. Mol Med Rep 2016;14:1742-50.
110. Du Y, Zhu M, Zhou X, et al. miR-20a enhances cisplatin resistance of human gastric cancer cell line by targeting NFKBIB. Tumour Biol 2016;37:1261-9.
111. Shao Q, Xu J, Guan X, et al. In vitro and in vivo effects of miRNA-19b/20a/92a on gastric cancer stem cells and the related mechanism. Int J Med Sci 2018;15:86-94.
112. Ishimoto T, Nagano O, Yae T, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 2011;19:387-400.
113. Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA. Aldehyde dehydrogenases and cell proliferation. Free Radic Biol Med 2012;52:735-46.
114. Wu D, Mou YP, Chen K, et al. Aldehyde dehydrogenase 3A1 is robustly upregulated in gastric cancer stem-like cells and associated with tumorigenesis. Int J Oncol 2016;49:611-22.
115. Ikeda J, Mamat S, Tian T, et al. Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells. Lab Invest 2012;92:606-14.
116. Aponte PM, Caicedo A. Stemness in cancer: stem cells, cancer stem cells, and their microenvironment. Stem Cells Int 2017;2017:5619472.
117. Gasparetto M, Smith CA. ALDHs in normal and malignant hematopoietic cells: potential new avenues for treatment of AML and other blood cancers. Chem Biol Interact 2017;276:46-51.
119. Chen T, You Y, Jiang H, Wang ZZ. Epithelial-mesenchymal transition (EMT): a biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol 2017;232:3261-72.
120. Stemmler MP, Eccles RL, Brabletz S, Brabletz T. Non-redundant functions of EMT transcription factors. Nat Cell Biol 2019;21:102-12.
121. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119:1420-8.
122. Eun K, Ham SW, Kim H. Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting. BMB Rep 2017;50:117-25.
123. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 2019;20:69-84.
124. Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 2017;14:611-29.
125. Wilson MM, Weinberg RA, Lees JA, Guen VJ. Emerging mechanisms by which EMT programs control stemness. Trends Cancer 2020;6:775-80.
126. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010;29:4741-51.
127. Ma X, Wang B, Wang X, Luo Y, Fan W. NANOGP8 is the key regulator of stemness, EMT, Wnt pathway, chemoresistance, and other malignant phenotypes in gastric cancer cells. PLoS One 2018;13:e0192436.
128. Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol 2016;11:47-76.
129. Saygin C, Matei D, Majeti R, Reizes O, Lathia JD. Targeting cancer stemness in the clinic: from hype to hope. Cell Stem Cell 2019;24:25-40.
130. Prager BC, Xie Q, Bao S, Rich JN. Cancer stem cells: the architects of the tumor ecosystem. Cell Stem Cell 2019;24:41-53.
131. Fiori ME, Di Franco S, Villanova L, Bianca P, Stassi G, De Maria R. Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance. Mol Cancer 2019;18:70.
132. Yu Y, Xiao CH, Tan LD, Wang QS, Li XQ, Feng YM. Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-β signalling. Br J Cancer 2014;110:724-32.
133. Choi YJ, Kim N, Chang H, et al. Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells. Carcinogenesis 2015;36:553-63.
134. Huang L, Wu RL, Xu AM. Epithelial-mesenchymal transition in gastric cancer. Am J Transl Res 2015;7:2141-58. [PMID: 26807164].
135. Han ME, Kim HJ, Shin DH, Hwang SH, Kang CD, Oh SO. Overexpression of NRG1 promotes progression of gastric cancer by regulating the self-renewal of cancer stem cells. J Gastroenterol 2015;50:645-56.
136. Loeffler M, Krüger JA, Niethammer AG, Reisfeld RA. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J Clin Invest 2006;116:1955-62.
137. Ma Y, Zhu J, Chen S, et al. Low expression of SPARC in gastric cancer-associated fibroblasts leads to stemness transformation and 5-fluorouracil resistance in gastric cancer. Cancer Cell Int 2019;19:137.
139. Kalluri R, LeBleu VS. function
141. Tai YL, Chen KC, Hsieh JT, Shen TL. Exosomes in cancer development and clinical applications. Cancer Sci 2018;109:2364-74.
142. Dai J, Su Y, Zhong S, et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther 2020;5:145.
143. Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018;560:382-6.
144. Poggio M, Hu T, Pai CC, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell 2019;177:414-427.e13.
145. Wang X, Qiao D, Chen L, et al. Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance. Mol Cancer 2019;18:182.
146. Wu S, Luo M, To KKW, et al. Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer. Mol Cancer 2021;20:17.
147. Wang J, Zheng Y, Zhao M. Exosome-based cancer therapy: implication for targeting cancer stem cells. Front Pharmacol 2016;7:533.
148. Lee NK, Kothandan VK, Kothandan S, Byun Y, Hwang SR. Exosomes and cancer stem cells in cancer immunity: current reports and future directions. Vaccines (Basel) 2021;9:441.
149. Zuo S, Yi Y, Wang C, et al. Extrachromosomal circular DNA (eccDNA): from chaos to function. Front Cell Dev Biol 2021;9:792555.
150. Wang M, Chen X, Yu F, Ding H, Zhang Y, Wang K. Extrachromosomal circular DNAs: origin, formation and emerging function in cancer. Int J Biol Sci 2021;17:1010-25.
151. Paulsen T, Kumar P, Koseoglu MM, Dutta A. Discoveries of extrachromosomal circles of DNA in normal and tumor cells. Trends Genet 2018;34:270-8.
152. Ling X, Han Y, Meng J, et al. Small extrachromosomal circular DNA (eccDNA): major functions in evolution and cancer. Mol Cancer 2021;20:113.
153. Curt GA, Carney DN, Cowan KH, et al. Unstable methotrexate resistance in human small-cell carcinoma associated with double minute chromosomes. N Engl J Med 1983;308:199-202.
154. Ruiz JC, Choi KH, von Hoff DD, Roninson IB, Wahl GM. Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line. Mol Cell Biol 1989;9:109-15.
155. Nathanson DA, Gini B, Mottahedeh J, et al. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 2014;343:72-6.
156. Nikolaev S, Santoni F, Garieri M, et al. Extrachromosomal driver mutations in glioblastoma and low-grade glioma. Nat Commun 2014;5:5690.
157. Cai M, Zhang H, Hou L, et al. Inhibiting homologous recombination decreases extrachromosomal amplification but has no effect on intrachromosomal amplification in methotrexate-resistant colon cancer cells. Int J Cancer 2019;144:1037-48.
159. Lin L, Wei H, Yi J, et al. Chronic CagA-positive Helicobacter pylori infection with MNNG stimulation synergistically induces mesenchymal and cancer stem cell-like properties in gastric mucosal epithelial cells. J Cell Biochem 2019;120:17635-49.
160. Song X, Xin N, Wang W, Zhao C. Wnt/β-catenin, an oncogenic pathway targeted by H. pylori in gastric carcinogenesis. Oncotarget 2015;6:35579-88.
161. Courtois S, Haykal M, Bodineau C, et al. Autophagy induced by Helicobacter pylori infection is necessary for gastric cancer stem cell emergence. Gastric Cancer 2021;24:133-44.
162. Tiffon C, Giraud J, Molina-Castro SE, et al. TAZ controls helicobacter pylori-induced epithelial-mesenchymal transition and cancer stem cell-like invasive and tumorigenic properties. Cells 2020;9:1462.
163. Oh JD, Karam SM, Gordon JI. Intracellular Helicobacter pylori in gastric epithelial progenitors. Proc Natl Acad Sci USA 2005;102:5186-91.
164. Giannakis M, Chen SL, Karam SM, Engstrand L, Gordon JI. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci USA 2008;105:4358-63.
165. Varon C, Dubus P, Mazurier F, et al. Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice. Gastroenterology 2012;142:281-91.
166. Korkaya H, Paulson A, Charafe-Jauffret E, et al. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol 2009;7:e1000121.
167. Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 2006;66:6063-71.
