Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

Shi-Yong Sun

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Front. Med. ›› 2022, Vol. 16 ›› Issue (5) : 701-713. DOI: 10.1007/s11684-022-0951-0
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Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

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Abstract

A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.

Keywords

acquired resistance / EGFR inhibitor / apoptosis / lung cancer

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Shi-Yong Sun. Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors. Front. Med., 2022, 16(5): 701‒713 https://doi.org/10.1007/s11684-022-0951-0

References

[1]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022; 72( 1): 7– 33
CrossRef Pubmed Google scholar
[2]
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71( 3): 209– 249
CrossRef Pubmed Google scholar
[3]
Tang ZH, Lu JJ. Osimertinib resistance in non-small cell lung cancer: mechanisms and therapeutic strategies. Cancer Lett 2018; 420 : 242– 246
CrossRef Pubmed Google scholar
[4]
Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 2020; 382( 1): 41– 50
CrossRef Pubmed Google scholar
[5]
Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378( 2): 113– 125
CrossRef Pubmed Google scholar
[6]
Lu S, Wang Q, Zhang G, Dong X, Yang CT, Song Y, Chang GC, Lu Y, Pan H, Chiu CH, Wang Z, Feng J, Zhou J, Xu X, Guo R, Chen J, Yang H, Chen Y, Yu Z, Shiah HS, Wang CC, Yang N, Fang J, Wang P, Wang K, Hu Y, He J, Wang Z, Shi J, Chen S, Wu Q, Sun C, Li C, Wei H, Cheng Y, Su WC, Hsia TC, Cui J, Sun Y, Ou SI, Zhu VW, Chih-Hsin Yang J. Efficacy of aumolertinib (HS-10296) in patients with advanced EGFR T790M+ NSCLC: updated post-national medical products administration approval results from the APOLLO registrational trial. J Thorac Oncol 2022; 17( 3): 411– 422
CrossRef Pubmed Google scholar
[7]
Romero D. Aumolertinib is effective in NSCLC. Nat Rev Clin Oncol 2022; 19( 1): 6
CrossRef Pubmed Google scholar
[8]
Schmid S, Li JJN, Leighl NB. Mechanisms of osimertinib resistance and emerging treatment options. Lung Cancer 2020; 147 : 123– 129
CrossRef Pubmed Google scholar
[9]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144( 5): 646– 674
CrossRef Pubmed Google scholar
[10]
Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov 2022; 12( 1): 31– 46
CrossRef Pubmed Google scholar
[11]
Diepstraten ST, Anderson MA, Czabotar PE, Lessene G, Strasser A, Kelly GL. The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs. Nat Rev Cancer 2022; 22( 1): 45– 64
CrossRef Pubmed Google scholar
[12]
Zimmermann KC, Green DR. How cells die: apoptosis pathways. J Allergy Clin Immunol 2001; 108( 4 Suppl): S99– S103
CrossRef Pubmed Google scholar
[13]
Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407( 6805): 770– 776
CrossRef Pubmed Google scholar
[14]
Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998; 281( 5381): 1305– 1308
CrossRef Pubmed Google scholar
[15]
Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 1999; 11( 2): 255– 260
CrossRef Pubmed Google scholar
[16]
Lavrik I, Golks A, Krammer PH. Death receptor signaling. J Cell Sci 2005; 118( 2): 265– 267
CrossRef Pubmed Google scholar
[17]
Krueger A, Baumann S, Krammer PH, Kirchhoff S. FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 2001; 21( 24): 8247– 8254
CrossRef Pubmed Google scholar
[18]
Budd RC, Yeh WC, Tschopp J. cFLIP regulation of lymphocyte activation and development. Nat Rev Immunol 2006; 6( 3): 196– 204
CrossRef Pubmed Google scholar
[19]
Wajant H. Targeting the FLICE Inhibitory Protein (FLIP) in cancer therapy. Mol Interv 2003; 3( 3): 124– 127
CrossRef Pubmed Google scholar
[20]
Kataoka T. The caspase-8 modulator c-FLIP. Crit Rev Immunol 2005; 25( 1): 31– 58
CrossRef Pubmed Google scholar
[21]
Kim Y, Suh N, Sporn M, Reed JC. An inducible pathway for degradation of FLIP protein sensitizes tumor cells to TRAIL-induced apoptosis. J Biol Chem 2002; 277( 25): 22320– 22329
CrossRef Pubmed Google scholar
[22]
Poukkula M, Kaunisto A, Hietakangas V, Denessiouk K, Katajamäki T, Johnson MS, Sistonen L, Eriksson JE. Rapid turnover of c-FLIPshort is determined by its unique C-terminal tail. J Biol Chem 2005; 280( 29): 27345– 27355
CrossRef Pubmed Google scholar
[23]
Chang L, Kamata H, Solinas G, Luo JL, Maeda S, Venuprasad K, Liu YC, Karin M. The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell 2006; 124( 3): 601– 613
CrossRef Pubmed Google scholar
[24]
Falschlehner C, Schaefer U, Walczak H. Following TRAIL’s path in the immune system. Immunology 2009; 127( 2): 145– 154
CrossRef Pubmed Google scholar
[25]
Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 2008; 8( 10): 782– 798
CrossRef Pubmed Google scholar
[26]
O’ Reilly E, Tirincsi A, Logue SE, Szegezdi E. The Janus face of death receptor signaling during tumor immunoediting. Front Immunol 2016; 7 : 446
CrossRef Pubmed Google scholar
[27]
Fairlie WD, Lee EF. Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers. Biochem Soc Trans 2021; 49( 5): 2397– 2410
CrossRef Pubmed Google scholar
[28]
Westaby D, Jimenez-Vacas JM, Padilha A, Varkaris A, Balk SP, de Bono JS, Sharp A. Targeting the intrinsic apoptosis pathway: a window of opportunity for prostate cancer. Cancers (Basel) 2021; 14( 1): 51
CrossRef Pubmed Google scholar
[29]
Shi P, Oh YT, Deng L, Zhang G, Qian G, Zhang S, Ren H, Wu G, Legendre B Jr, Anderson E, Ramalingam SS, Owonikoko TK, Chen M, Sun SY. Overcoming acquired resistance to AZD9291, a third-generation EGFR inhibitor, through modulation of MEK/ERK-dependent Bim and Mcl-1 degradation. Clin Cancer Res 2017; 23( 21): 6567– 6579
CrossRef Pubmed Google scholar
[30]
Ge X, Zhang Y, Huang F, Wu Y, Pang J, Li X, Fan F, Liu H, Li S. EGFR tyrosine kinase inhibitor almonertinib induces apoptosis and autophagy mediated by reactive oxygen species in non-small cell lung cancer cells. Hum Exp Toxicol 2021; 40( 12_suppl): S49– S62
CrossRef Pubmed Google scholar
[31]
Shi P, Zhang S, Zhu L, Qian G, Ren H, Ramalingam SS, Chen M, Sun SY. The third-generation EGFR inhibitor, osimertinib, promotes c-FLIP degradation, enhancing apoptosis including TRAIL-induced apoptosis in NSCLC cells with activating EGFR mutations. Transl Oncol 2019; 12( 5): 705– 713
CrossRef Pubmed Google scholar
[32]
Zhang S, Chen Z, Shi P, Fan S, He Y, Wang Q, Li Y, Ramalingam SS, Owonikoko TK, Sun SY. Downregulation of death receptor 4 is tightly associated with positive response of EGFR mutant lung cancer to EGFR-targeted therapy and improved prognosis. Theranostics 2021; 11( 8): 3964– 3980
CrossRef Pubmed Google scholar
[33]
Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E, Tiseo M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer 2019; 121( 9): 725– 737
CrossRef Pubmed Google scholar
[34]
Weng CH, Chen LY, Lin YC, Shih JY, Lin YC, Tseng RY, Chiu AC, Yeh YH, Liu C, Lin YT, Fang JM, Chen CC. Epithelial-mesenchymal transition (EMT) beyond EGFR mutations per se is a common mechanism for acquired resistance to EGFR TKI. Oncogene 2019; 38( 4): 455– 468
CrossRef Pubmed Google scholar
[35]
Yochum ZA, Cades J, Wang H, Chatterjee S, Simons BW, O’Brien JP, Khetarpal SK, Lemtiri-Chlieh G, Myers KV, Huang EH, Rudin CM, Tran PT, Burns TF. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 2019; 38( 5): 656– 670
CrossRef Pubmed Google scholar
[36]
Chang TH, Tsai MF, Su KY, Wu SG, Huang CP, Yu SL, Yu YL, Lan CC, Yang CH, Lin SB, Wu CP, Shih JY, Yang PC. Slug confers resistance to the epidermal growth factor receptor tyrosine kinase inhibitor. Am J Respir Crit Care Med 2011; 183( 8): 1071– 1079
CrossRef Pubmed Google scholar
[37]
Song KA, Niederst MJ, Lochmann TL, Hata AN, Kitai H, Ham J, Floros KV, Hicks MA, Hu H, Mulvey HE, Drier Y, Heisey DAR, Hughes MT, Patel NU, Lockerman EL, Garcia A, Gillepsie S, Archibald HL, Gomez-Caraballo M, Nulton TJ, Windle BE, Piotrowska Z, Sahingur SE, Taylor SM, Dozmorov M, Sequist LV, Bernstein B, Ebi H, Engelman JA, Faber AC. Epithelial-to-mesenchymal transition antagonizes response to targeted therapies in lung cancer by suppressing BIM. Clin Cancer Res 2018; 24( 1): 197– 208
CrossRef Pubmed Google scholar
[38]
Qin Q, Li X, Liang X, Zeng L, Wang J, Sun L, Zhong D. Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR-mutant non-small cell lung cancer. Thorac Cancer 2021; 12( 11): 1708– 1715
CrossRef Pubmed Google scholar
[39]
Jiang XM, Xu YL, Yuan LW, Zhang LL, Huang MY, Ye ZH, Su MX, Chen XP, Zhu H, Ye RD, Lu JJ. TGFβ2-mediated epithelial-mesenchymal transition and NF-κB pathway activation contribute to osimertinib resistance. Acta Pharmacol Sin 2021; 42( 3): 451– 459
CrossRef Pubmed Google scholar
[40]
Faber AC, Corcoran RB, Ebi H, Sequist LV, Waltman BA, Chung E, Incio J, Digumarthy SR, Pollack SF, Song Y, Muzikansky A, Lifshits E, Roberge S, Coffman EJ, Benes CH, Gómez HL, Baselga J, Arteaga CL, Rivera MN, Dias-Santagata D, Jain RK, Engelman JA. BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors. Cancer Discov 2011; 1( 4): 352– 365
CrossRef Pubmed Google scholar
[41]
Costa C, Molina MA, Drozdowskyj A, Giménez-Capitán A, Bertran-Alamillo J, Karachaliou N, Gervais R, Massuti B, Wei J, Moran T, Majem M, Felip E, Carcereny E, Garcia-Campelo R, Viteri S, Taron M, Ono M, Giannikopoulos P, Bivona T, Rosell R. The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial. Clin Cancer Res 2014; 20( 7): 2001– 2010
CrossRef Pubmed Google scholar
[42]
Ng KP, Hillmer AM, Chuah CT, Juan WC, Ko TK, Teo AS, Ariyaratne PN, Takahashi N, Sawada K, Fei Y, Soh S, Lee WH, Huang JW, Allen JC Jr, Woo XY, Nagarajan N, Kumar V, Thalamuthu A, Poh WT, Ang AL, Mya HT, How GF, Yang LY, Koh LP, Chowbay B, Chang CT, Nadarajan VS, Chng WJ, Than H, Lim LC, Goh YT, Zhang S, Poh D, Tan P, Seet JE, Ang MK, Chau NM, Ng QS, Tan DS, Soda M, Isobe K, Nöthen MM, Wong TY, Shahab A, Ruan X, Cacheux-Rataboul V, Sung WK, Tan EH, Yatabe Y, Mano H, Soo RA, Chin TM, Lim WT, Ruan Y, Ong ST. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 2012; 18( 4): 521– 528
CrossRef Pubmed Google scholar
[43]
Isobe K, Kakimoto A, Mikami T, Kaburaki K, Kobayashi H, Yoshizawa T, Makino T, Otsuka H, Sano GO, Sugino K, Sakamoto S, Takai Y, Tochigi N, Iyoda A, Homma S. Association of BIM deletion polymorphism and BIM-γ RNA expression in NSCLC with EGFR mutation. Cancer Genomics Proteomics 2016; 13( 6): 475– 482
CrossRef Pubmed Google scholar
[44]
Wu SG, Liu YN, Yu CJ, Yang PC, Shih JY. Association of BIM deletion polymorphism with intrinsic resistance to EGFR tyrosine kinase inhibitors in patients with lung adenocarcinoma. JAMA Oncol 2016; 2( 6): 826– 828
CrossRef Pubmed Google scholar
[45]
Isobe K, Hata Y, Tochigi N, Kaburaki K, Kobayashi H, Makino T, Otsuka H, Sato F, Ishida F, Kikuchi N, Hirota N, Sato K, Sano G, Sugino K, Sakamoto S, Takai Y, Shibuya K, Iyoda A, Homma S. Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation. J Thorac Oncol 2014; 9( 4): 483– 487
CrossRef Pubmed Google scholar
[46]
Lee JK, Shin JY, Kim S, Lee S, Park C, Kim JY, Koh Y, Keam B, Min HS, Kim TM, Jeon YK, Kim DW, Chung DH, Heo DS, Lee SH, Kim JI. Primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer harboring TKI-sensitive EGFR mutations: an exploratory study. Ann Oncol 2013; 24( 8): 2080– 2087
CrossRef Pubmed Google scholar
[47]
Tanimoto A, Takeuchi S, Arai S, Fukuda K, Yamada T, Roca X, Ong ST, Yano S. Histone deacetylase 3 inhibition overcomes BIM deletion polymorphism-mediated osimertinib resistance in EGFR-mutant lung cancer. Clin Cancer Res 2017; 23( 12): 3139– 3149
CrossRef Pubmed Google scholar
[48]
Li X, Zhang D, Li B, Zou B, Wang S, Fan B, Li W, Yu J, Wang L. Clinical implications of germline BCL2L11 deletion polymorphism in pretreated advanced NSCLC patients with osimertinib therapy. Lung Cancer 2021; 151 : 39– 43
CrossRef Pubmed Google scholar
[49]
Isobe K, Yoshizawa T, Sekiya M, Miyoshi S, Nakamura Y, Urabe N, Isshiki T, Sakamoto S, Takai Y, Tomida T, Adachi-Akahane S, Iyoda A, Homma S, Kishi K. Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer. Respir Investig 2021; 59( 4): 535– 544
CrossRef Pubmed Google scholar
[50]
Chen S, Fu L, Raja SM, Yue P, Khuri FR, Sun SY. Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis. Mol Cancer 2010; 9( 1): 23
CrossRef Pubmed Google scholar
[51]
Hartwig T, Montinaro A, von Karstedt S, Sevko A, Surinova S, Chakravarthy A, Taraborrelli L, Draber P, Lafont E, Arce Vargas F, El-Bahrawy MA, Quezada SA, Walczak H. The TRAIL-induced cancer secretome promotes a tumor-supportive immune microenvironment via CCR2. Mol Cell 2017; 65( 4): 730– 742.e5
CrossRef Pubmed Google scholar
[52]
Henry CM, Martin SJ. Caspase-8 acts in a non-enzymatic role as a scaffold for assembly of a pro-inflammatory “FADDosome” complex upon TRAIL stimulation. Mol Cell 2017; 65( 4): 715– 729.e5
CrossRef Pubmed Google scholar
[53]
Li Y, Zang H, Qian G, Owonikoko TK, Ramalingam SR, Sun SY. ERK inhibition effectively overcomes acquired resistance of epidermal growth factor receptor-mutant non-small cell lung cancer cells to osimertinib. Cancer 2020; 126( 6): 1339– 1350
CrossRef Pubmed Google scholar
[54]
Jiang W, Cai F, Xu H, Lu Y, Chen J, Liu J, Cao N, Zhang X, Chen X, Huang Q, Zhuang H, Hua ZC. Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner. Protein Cell 2020; 11( 11): 825– 845
CrossRef Pubmed Google scholar
[55]
Jiang J, Zhao LG, Teng YJ, Chen SL, An LP, Ma JL, Wang J, Xia YY. ERK5 signalling pathway is essential for fluid shear stress-induced COX-2 gene expression in MC3T3-E1 osteoblast. Mol Cell Biochem 2015; 406( 1–2): 237– 243
CrossRef Pubmed Google scholar
[56]
Liang Z, Xie W, Wu R, Geng H, Zhao L, Xie C, Li X, Huang C, Zhu J, Zhu M, Zhu W, Wu J, Geng S, Zhong C. ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial-mesenchymal transition. Oncotarget 2015; 6( 23): 19605– 19618
CrossRef Pubmed Google scholar
[57]
Park SJ, Choi YS, Lee S, Lee YJ, Hong S, Han S, Kim BC. BIX02189 inhibits TGF-β1-induced lung cancer cell metastasis by directly targeting TGF-β type I receptor. Cancer Lett 2016; 381( 2): 314– 322
CrossRef Pubmed Google scholar
[58]
Zhao W, Yu D, Chen Z, Yao W, Yang J, Ramalingam SS, Sun SY. Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to the third generation EGFR inhibitor, osimertinib, via enhancing Bim-dependent apoptosis. Cancer Lett 2021; 519 : 141– 149
CrossRef Pubmed Google scholar
[59]
Zang H, Qian G, Zong D, Fan S, Owonikoko TK, Ramalingam SS, Sun SY. Overcoming acquired resistance of epidermal growth factor receptor-mutant non-small cell lung cancer cells to osimertinib by combining osimertinib with the histone deacetylase inhibitor panobinostat (LBH589). Cancer 2020; 126( 9): 2024– 2033
CrossRef Pubmed Google scholar
[60]
Cao F, Gong YB, Kang XH, Lu ZH, Wang Y, Zhao KL, Miao ZH, Liao MJ, Xu ZY. Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer. Toxicol Appl Pharmacol 2019; 379 : 114662
CrossRef Pubmed Google scholar
[61]
Zang H, Qian G, Arbiser J, Owonikoko TK, Ramalingam SS, Fan S, Sun SY. Overcoming acquired resistance of EGFR-mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib, with the natural product honokiol. Mol Oncol 2020; 14( 4): 882– 895
CrossRef Pubmed Google scholar
[62]
Chen Z, Vallega KA, Chen H, Zhou J, Ramalingam SS, Sun SY. The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition. Pharmacol Res 2022; 175 : 105998
CrossRef Pubmed Google scholar
[63]
Han R, Hao S, Lu C, Zhang C, Lin C, Li L, Wang Y, Hu C, He Y. Aspirin sensitizes osimertinib-resistant NSCLC cells in vitro and in vivo via Bim-dependent apoptosis induction. Mol Oncol 2020; 14( 6): 1152– 1169
CrossRef Pubmed Google scholar
[64]
Chen Z, Yu D, Owonikoko TK, Ramalingam SS, Sun SY. Induction of SREBP1 degradation coupled with suppression of SREBP1-mediated lipogenesis impacts the response of EGFR mutant NSCLC cells to osimertinib. Oncogene 2021; 40( 49): 6653– 6665
CrossRef Pubmed Google scholar
[65]
Zhu L, Chen Z, Zang H, Fan S, Gu J, Zhang G, Sun KD, Wang Q, He Y, Owonikoko TK, Ramalingam SS, Sun SY. Targeting c-Myc to overcome acquired resistance of EGFR mutant NSCLC cells to the third-generation EGFR tyrosine kinase inhibitor, osimertinib. Cancer Res 2021; 81( 18): 4822– 4834
CrossRef Pubmed Google scholar
[66]
Tanaka K, Yu HA, Yang S, Han S, Selcuklu SD, Kim K, Ramani S, Ganesan YT, Moyer A, Sinha S, Xie Y, Ishizawa K, Osmanbeyoglu HU, Lyu Y, Roper N, Guha U, Rudin CM, Kris MG, Hsieh JJ, Cheng EH. Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis. Cancer Cell 2021; 39( 9): 1245– 1261.e6
CrossRef Pubmed Google scholar
[67]
Watanabe S, Yoshida T, Kawakami H, Takegawa N, Tanizaki J, Hayashi H, Takeda M, Yonesaka K, Tsurutani J, Nakagawa K. T790M-selective EGFR-TKI combined with dasatinib as an optimal strategy for overcoming EGFR-TKI resistance in T790M-positive non-small cell lung cancer. Mol Cancer Ther 2017; 16( 11): 2563– 2571
CrossRef Pubmed Google scholar
[68]
Ma G, Deng Y, Qian L, Vallega KA, Zhang G, Deng X, Owonikoko TK, Ramalingam SS, Fang DD, Zhai Y, Sun SY. Overcoming acquired resistance to third-generation EGFR inhibitors by targeting activation of intrinsic apoptotic pathway through Mcl-1 inhibition, Bax activation, or both. Oncogene 2022; 41( 12): 1691– 1700
CrossRef Pubmed Google scholar
[69]
Lu Y, Bian D, Zhang X, Zhang H, Zhu Z. Inhibition of Bcl-2 and Bcl-xL overcomes the resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer. Mol Med Rep 2021; 23( 1): 48
CrossRef Pubmed Google scholar
[70]
Liu Z, Gao W. Synergistic effects of Bcl-2 inhibitors with AZD9291 on overcoming the acquired resistance of AZD9291 in H1975 cells. Arch Toxicol 2020; 94( 9): 3125– 3136
CrossRef Pubmed Google scholar
[71]
Suda K, Mitsudomi T. Drug tolerance to EGFR tyrosine kinase inhibitors in lung cancers with EGFR mutations. Cells 2021; 10( 7): 1590
CrossRef Pubmed Google scholar
[72]
Cabanos HF, Hata AN. Emerging insights into targeted therapy-tolerant persister cells in cancer. Cancers (Basel) 2021; 13( 11): 2666
CrossRef Pubmed Google scholar
[73]
Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 2010; 141( 1): 69– 80
CrossRef Pubmed Google scholar
[74]
Hata AN, Niederst MJ, Archibald HL, Gomez-Caraballo M, Siddiqui FM, Mulvey HE, Maruvka YE, Ji F, Bhang HE, Krishnamurthy Radhakrishna V, Siravegna G, Hu H, Raoof S, Lockerman E, Kalsy A, Lee D, Keating CL, Ruddy DA, Damon LJ, Crystal AS, Costa C, Piotrowska Z, Bardelli A, Iafrate AJ, Sadreyev RI, Stegmeier F, Getz G, Sequist LV, Faber AC, Engelman JA. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med 2016; 22( 3): 262– 269
CrossRef Pubmed Google scholar
[75]
Kurppa KJ, Liu Y, To C, Zhang T, Fan M, Vajdi A, Knelson EH, Xie Y, Lim K, Cejas P, Portell A, Lizotte PH, Ficarro SB, Li S, Chen T, Haikala HM, Wang H, Bahcall M, Gao Y, Shalhout S, Boettcher S, Shin BH, Thai T, Wilkens MK, Tillgren ML, Mushajiang M, Xu M, Choi J, Bertram AA, Ebert BL, Beroukhim R, Bandopadhayay P, Awad MM, Gokhale PC, Kirschmeier PT, Marto JA, Camargo FD, Haq R, Paweletz CP, Wong KK, Barbie DA, Long HW, Gray NS, Jänne PA. Treatment-induced tumor dormancy through YAP-mediated transcriptional reprogramming of the apoptotic pathway. Cancer Cell 2020; 37( 1): 104– 122.e12
CrossRef Pubmed Google scholar
[76]
Gu J, Yang W, Shi P, Zhang G, Owonikoko TK, Ramalingam SR, Sun SY. MEK or ERK inhibition effectively abrogates emergence of acquired osimertinib resistance in the treatment of epidermal growth factor receptor-mutant lung cancers. Cancer 2020; 126 : 3788– 3799
CrossRef Pubmed Google scholar
[77]
Cotter TG. Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer 2009; 9( 7): 501– 507
CrossRef Pubmed Google scholar
[78]
Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 2005; 5( 11): 876– 885
CrossRef Pubmed Google scholar

Acknowledgements

I am thankful to Dr. Anthea Hammond in my department for editing the manuscript. Some of work done in my laboratory were supported by the NIH/NCI R01 CA223220, R01 CA245386, UG1 CA233259 awards and Emory University Winship Cancer Institute lung cancer pilot funds. Shi-Yong Sun is a Georgia Research Alliance Distinguished Cancer Scientist.

Compliance with ethics guidelines

Shi-Yong Sun declares no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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