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Review

Tackling Drug Resistance in EGFR Exon 20 Insertion Mutant Lung Cancer

, , , , &
Pages 301-317 | Published online: 09 Mar 2021

References

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi:10.3322/caac.21262
  • Duma N, Santana-Davila R, Molina JR. Non–small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 2019;94(8):1623–1640. doi:10.1016/j.mayocp.2019.01.013
  • Pakkala S, Ramalingam SS. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3:15. doi:10.1172/jci.insight.120858
  • D’Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol. 2011;29(15):2066–2070. doi:10.1200/JCO.2010.32.6181
  • Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179–184. doi:10.1097/JTO.0b013e3182779d18
  • Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 2012;13(1):23–31. doi:10.1016/S1470-2045(11)70129-2
  • Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol. 2020;61:167–179. doi:10.1016/j.semcancer.2019.09.015
  • Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduct Target Ther. 2019;4(1):5. doi:10.1038/s41392-019-0038-9
  • Robichaux JP, Elamin YY, Tan Z, et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med. 2018;24(5):638–646. doi:10.1038/s41591-018-0007-9
  • Udager AM, Rolland DCM, McHugh JB, et al. High-frequency targetable EGFR mutations in sinonasal squamous cell carcinomas arising from inverted sinonasal papilloma. Cancer Res. 2015;75(13):2600–2606. doi:10.1158/0008-5472.CAN-15-0340
  • Madison RW, Gupta SV, Elamin YY, et al. Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions. BJU Int. 2020;125(5):739–746. doi:10.1111/bju.15006
  • Weinstein IB, Joe A. Oncogene addiction. Cancer Res. 2008;68(9):3077–3080. doi:10.1158/0008-5472.CAN-07-3293
  • Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220–229. doi:10.1158/1535-7163.MCT-12-0620
  • Yasuda H, Park E, Yun CH, et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med. 2013;5(216):216ra177. doi:10.1126/scitranslmed.3007205
  • Voon PJ, Tsui DWY, Rosenfeld N, Chin TM. Letter to Editor: EGFR Exon 20 Insertion A763-Y764insFQEA and response to Erlotinib. Mol Cancer Ther. 2013;12:20–25. doi:10.1158/1535-7163.MCT-13-0192
  • Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. N Engl J Med. 2002;346(2):92–98. doi:10.1056/nejmoa011954
  • Noronha V, Choughule A, Patil VM, et al. Epidermal growth factor receptor exon 20 mutation in lung cancer: types, incidence, clinical features and impact on treatment. Onco Targets Ther. 2017;10:2903–2908. doi:10.2147/OTT.S133245
  • Yang G, Li J, Xu H, et al. EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: molecular heterogeneity and treatment outcome from nationwide real-world study. Lung Cancer. 2020;145:186–194. doi:10.1016/j.lungcan.2020.03.014
  • Doebele RC, Riely GJ, Spira AI, et al. First report of safety, PK, and preliminary antitumor activity of the oral EGFR/HER2 exon 20 inhibitor TAK-788 (AP32788) in non–small cell lung cancer (NSCLC). J Clin Oncol. 2018;36(suppl):abstr 9015.
  • Udagawa H, Hasako S, Ohashi A, et al. TAS6417/CLN-081 Is a pan-mutation-selective EGFR tyrosine kinase inhibitor with a broad spectrum of preclinical activity against clinically relevant EGFR mutations. Mol Cancer Res. 2019;17(11):2233–2243. doi:10.1158/1541-7786.MCR-19-0419
  • Park K, John T, Kim S-W, et al. Amivantamab (JNJ-61186372), an anti-EGFR-MET bispecific antibody, in patients with EGFR exon 20 insertion (exon20ins)-mutated non-small cell lung cancer (NSCLC). J Clin Oncol. 2020;38(15_suppl):9512. doi:10.1200/jco.2020.38.15_suppl.9512
  • Piotrowska Z, Costa DB, Oxnard GR, et al. Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions. Ann Oncol. 2018;29(10):2092–2097. doi:10.1093/annonc/mdy336
  • Gonzalvez F. TAK-788: an EGFR inhibitor, currently in Phase II clinical trials, targeting lung cancers with Exon20 insertion mutations. AACR 2020; 2020:DDT02–03. Availalble from: https://www.abstractsonline.com/pp8/#!/9045/presentation/6845. Accessed May 14, 2020.
  • Elamin Y, Robichaux J, Heymach J. Preliminary results of a Phase II study of poziotinib in EGFR Exon 20 mutant advanced NSCLC. J Thorac Oncol. 2017;12(8):S1536. doi:10.1016/j.jtho.2017.06.020
  • Heymach J, Negrao M, Robichaux J, et al. OA02.06 A Phase II Trial of Poziotinib in EGFR and HER2 exon 20 mutant Non-Small Cell Lung Cancer (NSCLC). AACR. 2020;(10):S323–S324. doi:10.1016/j.jtho.2018.08.243
  • Leduc C, Merlio JP, Besse B, et al. Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program. Ann Oncol. 2017;28(11):2715–2724. doi:10.1093/annonc/mdx404
  • Le X, Goldman JW, Clarke JM, et al. Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients. J Clin Oncol. 2020;38(15_suppl):9514. doi:10.1200/jco.2020.38.15_suppl.9514
  • Janne PA, Neal JW, Camidge DR, et al. Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions. J Clin Oncol. 2019;37(15_suppl):9007. doi:10.1200/JCO.2019.37.15_suppl.9007
  • ClinicalTrials.gov. TAK-788 as first-line treatment versus platinum-based chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 insertion mutations. Available from: https://clinicaltrials.gov/ct2/show/NCT04129502. Accessed Dec 15, 2020.
  • Hasako S, Terasaka M, Abe N, et al. TAS6417, A novel EGFR inhibitor targeting Exon 20 insertion mutations. Mol Cancer Ther. 2018;17(8):1648–1658. doi:10.1158/1535-7163.MCT-17-1206
  • Yun J, Lee S-H, Kim S-Y, et al. Antitumor activity of amivantamab (JNJ-61186372), an EGFR-cMet bispecific antibody, in diverse models of EGFR Exon 20 insertion-driven NSCLC. Cancer Discov. 2020. doi:10.1158/2159-8290.CD-20-0116
  • A study of combination amivantamab and carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in participants with advanced or metastatic non-small cell lung cancer characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 insertions - full text view - ClinicalTrials.gov. Availalble from: https://clinicaltrials.gov/ct2/show/NCT04538664?term=amivantamab&draw=2&rank=1. Accessed January 28, 2021.
  • Felip E, Barlesi F, Besse B, et al. Phase 2 study of the HSP-90 Inhibitor AUY922 in previously treated and molecularly defined patients with advanced non–small cell lung cancer. J Thorac Oncol. 2018;13(4):576–584. doi:10.1016/j.jtho.2017.11.131
  • Jorge SE, Lucena-Araujo AR, Yasuda H, et al. EGFR Exon 20 insertion mutations display sensitivity to Hsp90 inhibition in preclinical models and lung adenocarcinomas. Clin Cancer Res. 2018;24:6548–6555. doi:10.1158/1078-0432.CCR-18-1541
  • Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–246. doi:10.1016/s1470-2045(11)70393-x
  • Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947–957. doi:10.1056/NEJMoa0810699
  • Soria J-C, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR -mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113–125. doi:10.1056/NEJMoa1713137
  • Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2017;376(7):629–640. doi:10.1056/nejmoa1612674
  • Elamin Y, Robichaux J, Carter B, et al. MA09.03 identification of mechanisms of acquired resistance to poziotinib in EGFR Exon 20 mutant Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol. 2019;14(10):S282–S283. doi:10.1016/j.jtho.2019.08.567
  • Riess JW, Gandara DR, Frampton GM, et al. Diverse EGFR Exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thorac Oncol. 2018;13(10):1560–1568. doi:10.1016/j.jtho.2018.06.019
  • Montenegro GB, Nagasaka M, Ma P, et al. P2.01-100 spectrum of EGFR Exon 20 insertion mutations and co-occurring genetic alterations in patients with non-small-cell lung cancer. J Thorac Oncol. 2019;14(10):S680. doi:10.1016/j.jtho.2019.08.1443
  • Yun C-H, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci. 2008;105(6):2070–2075. doi:10.1073/pnas.0709662105
  • Yosaatmadja Y, Silva S, Dickson JM, et al. Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed. J Struct Biol. 2015;192(3):539–544. doi:10.1016/j.jsb.2015.10.018
  • Zhou W, Ercan D, Chen L, et al. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2010;462(7276):1070–1074. doi:10.1038/nature08622
  • Ramalingam SS, Cheng Y, Zhou C, et al. Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study. Ann Oncol. 2018;29:viii740. doi:10.1093/annonc/mdy424.063
  • Butterworth S, Cross DAE, Finlay MRV, Ward RA, Waring MJ. The structure-guided discovery of osimertinib: the first U.S. FDA approved mutant selective inhibitor of EGFR T790M. Medchemcomm. 2017;8(5):820–822. doi:10.1039/c7md90012k
  • Thress KS, Paweletz CP, Felip E, et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015;21(6):560–562. doi:10.1038/nm.3854
  • Ercan D, Choi HG, Yun C-H, et al. EGFR mutations and resistance to irreversible pyrimidine-based EGFR inhibitors. Clin Cancer Res. 2015;21(17):3913–3923. doi:10.1158/1078-0432.CCR-14-2789
  • Chouitar J, Vincent S, Brake R, Li S. P2.13-32 TAK-788 is a novel and potent tyrosine kinase inhibitor with selective activity against EGFR/HER2. J Thorac Oncol. 2018;13(10):S811. doi:10.1016/j.jtho.2018.08.1427
  • Koga T, Kobayashi Y, Tomizawa K, et al. Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study. Lung Cancer. 2018;126:72–79. doi:10.1016/j.lungcan.2018.10.019
  • Shimamura T, Shapiro GI. Heat shock protein 90 inhibition in lung cancer. J Thorac Oncol. 2008;3(6 SUPPL 2):152–159. doi:10.1097/JTO.0b013e318174ea3a
  • Xu W, Soga S, Beebe K, et al. Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition. Br J Cancer. 2007;97(6):741–744. doi:10.1038/sj.bjc.6603950
  • Qin Q, Li X, Liang X, et al. CDK46 inhibitor palbociclib overcomes acquired resistance to third-generation EGFR inhibitor osimertinib in non-small cell lung cancer (NSCLC). Thorac Cancer. 2020;11(9):2389–2397. doi:10.1111/1759-7714.13521
  • Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316(5827):1039–1043. doi:10.1126/science.1141478
  • Shien K, Toyooka S, Yamamoto H, et al. Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res. 2015;73(10):3051–3061. doi:10.1158/0008-5472.CAN-12-4136
  • Weng CH, Chen LY, Lin YC, et al. 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. doi:10.1038/s41388-018-0454-2
  • Song KA, Niederst MJ, Lochmann TL, et al. Epithelial-to-mesenchymal transition antagonizes response to targeted therapies in lung cancer by suppressing BIM. Clin Cancer Res. 2018;24(1):197–208. doi:10.1158/1078-0432.CCR-17-1577
  • Vad-Nielsen J, Gammelgaard KR, Daugaard TF, Nielsen AL. Cause-and-effect relationship between FGFR1 expression and epithelial-mesenchymal transition in EGFR-mutated non-small cell lung cancer cells. Lung Cancer. 2019;132:132–140. doi:10.1016/j.lungcan.2019.04.023
  • Ware KE, Hinz TK, Kleczko E, et al. A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis. 2013;2(3):e39–e39. doi:10.1038/oncsis.2013.4
  • Jakobsen KR, Demuth C, Madsen AT, et al. MET amplification and epithelial-to-mesenchymal transition exist as parallel resistance mechanisms in erlotinib-resistant, EGFR-mutated, NSCLC HCC827 cells. Oncogenesis. 2017;6(4):e307. doi:10.1038/oncsis.2017.17
  • Bivona TG, Doebele RC. A framework for understanding and targeting residual disease in oncogene-driven solid cancers. Nat Med. 2016;22(5):472–478. doi:10.1038/nm.4091
  • Sharma SV, Lee DY, Li B, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141(1):69–80. doi:10.1016/j.cell.2010.02.027
  • Chen J, Li Y, Yu TS, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488(7412):522–526. doi:10.1038/nature11287
  • Fallahi‐Sichani M, Becker V, Izar B, et al. Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de‐differentiated state. Mol Syst Biol. 2017;13(1):905. doi:10.15252/msb.20166796
  • Su Y, Wei W, Robert L, et al. Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance. Proc Natl Acad Sci U S A. 2017;114(52):13679–13684. doi:10.1073/pnas.1712064115
  • Liau BB, Sievers C, Donohue LK, et al. Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance. Cell Stem Cell. 2017;20(2):233–246.e7. doi:10.1016/j.stem.2016.11.003
  • Jordan NV, Bardia A, Wittner BS, et al. HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature. 2016;537(7618):102–106. doi:10.1038/nature19328
  • Roesch A, Vultur A, Bogeski I, et al. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1Bhigh cells. Cancer Cell. 2013;23(6):811–825. doi:10.1016/j.ccr.2013.05.003
  • Roesch A, Fukunaga-Kalabis M, Schmidt EC, et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell. 2010;141(4):583–594. doi:10.1016/j.cell.2010.04.020
  • Kurata T, Tamura K, Kaneda H, et al. Effect of re-treatment with gefitinib (“Iressa”, ZD1839) after acquisition of resistance [1]. Ann Oncol. 2004;15(1):173. doi:10.1093/annonc/mdh006
  • Oh IJ, Ban HJ, Kim KS, Kim YC. Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer. 2012;77(1):121–127. doi:10.1016/j.lungcan.2012.01.012
  • Hata AN, Niederst MJ, Archibald HL, et al. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med. 2016;22(3):262–269. doi:10.1038/nm.4040
  • Ramirez M, Rajaram S, Steininger RJ, et al. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. Nat Commun. 2016;7:10690. doi:10.1038/ncomms10690
  • Burslem GM, Crews CM. Proteolysis-targeting chimeras as therapeutics and tools for biological discovery. Cell. 2020;181(1):102–114. doi:10.1016/j.cell.2019.11.031
  • Hu B, Zhou Y, Sun D, et al. PROTACs: new method to degrade transcription regulating proteins. Eur J Med Chem. 2020:207. doi:10.1016/j.ejmech.2020.112698.
  • An S, Fu L. Small-molecule PROTACs: an emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018;36:553–562. doi:10.1016/j.ebiom.2018.09.005
  • Burslem GM, Smith BE, Lai AC, Crew AP, Hines J, Crews Correspondence CM. The advantages of targeted protein degradation over inhibition: an RTK case study. Cell Chem Biol. 2018;25(67–77.e3):67–77.e3. doi:10.1016/j.chembiol.2017.09.009
  • Zhang H, Zhao HY, Xi XX, et al. Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC). Eur J Med Chem. 2020:189. doi:10.1016/j.ejmech.2020.112061.
  • Zorba A, Nguyen C, Xu Y, et al. Delineating the role of cooperativity in the design of potent PROTACs for BTK. Proc Natl Acad Sci U S A. 2018;115(31):E7285–E7292. doi:10.1073/pnas.1803662115
  • Matyskiela ME, Lu G, Ito T, et al. A novel cereblon modulator recruits GSPT1 to the CRL4 CRBN ubiquitin ligase. Nature. 2016;535(7611):252–257. doi:10.1038/nature18611
  • He Y, Khan S, Huo Z, et al. Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies. J Hematol Oncol. 2020;13(1):1–24. doi:10.1186/s13045-020-00924-z
  • Bondeson DP, Smith BE, Burslem GM, et al. Lessons in PROTAC design from selective degradation with a promiscuous warhead. Cell Chem Biol. 2018;25(1):78–87.e5. doi:10.1016/j.chembiol.2017.09.010
  • Hsu JHR, Rasmusson T, Robinson J, et al. EED-targeted PROTACs degrade EED, EZH2, and SUZ12 in the PRC2 Complex. Cell Chem Biol. 2020;27(1):41–46.e17. doi:10.1016/j.chembiol.2019.11.004
  • Moreau K, Coen M, Zhang AX, et al. Proteolysis‐targeting chimeras in drug development: a safety perspective. Br J Pharmacol. 2020;177(8):1709–1718. doi:10.1111/bph.15014
  • Ishoey M, Chorn S, Singh N, et al. Translation termination factor GSPT1 is a phenotypically relevant off-target of heterobifunctional phthalimide degraders. ACS Chem Biol. 2018;13(3):553–560. doi:10.1021/acschembio.7b00969
  • Gasic I, Groendyke BJ, Nowak RP, et al. Tubulin resists degradation by cereblon-recruiting PROTACs. Cells. 2020;9:5. doi:10.3390/cells9051083
  • Petschnigg J, Groisman B, Kotlyar M, et al. The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells. Nat Methods. 2014;11(5):585–592. doi:10.1038/nmeth.2895
  • Saraon P, Snider J, Kalaidzidis Y, et al. A drug discovery platform to identify compounds that inhibit EGFR triple mutants. Nat Chem Biol. 2020;16:577–586. doi:10.1038/s41589-020-0484-2
  • Li S, Schmitz KR, Jeffrey PD, Wiltzius JJW, Kussie P, Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell. 2005;7(4):301–311. doi:10.1016/j.ccr.2005.03.003
  • Gaborit N, Abdul-Haia A, Mancini M, et al. Examination of HER3 targeting in cancer using monoclonal antibodies. Proc Natl Acad Sci U S A. 2015;112(3):839–844. doi:10.1073/pnas.1423645112
  • Mancini M, Gal H, Gaborit N, et al. An oligoclonal antibody durably overcomes resistance of lung cancer to third‐generation EGFR inhibitors. EMBO Mol Med. 2018;10(2):294–308. doi:10.15252/emmm.201708076
  • Romaniello D, Mazzeo L, Mancini M, et al. A combination of approved antibodies overcomes resistance of lung cancer to osimertinib by blocking bypass pathways. Clin Cancer Res. 2018;24(22):5610–5621. doi:10.1158/1078-0432.CCR-18-0450
  • van Veggel B, de Langen AJ, Hashemi SMS, et al. Afatinib and cetuximab in four patients with EGFR Exon 20 insertion–positive advanced NSCLC. J Thorac Oncol. 2018;13(8):1222–1226. doi:10.1016/j.jtho.2018.04.012
  • Rusan M, Li K, Li Y, et al. Suppression of adaptive responses to targeted cancer therapy by transcriptional repression. Cancer Discov. 2018;8(1):59–73. doi:10.1158/2159-8290.CD-17-0461
  • Terai H, Kitajima S, Potter DS, et al. ER stress signaling promotes the survival of cancer “Persister Cells” tolerant to EGFR tyrosine Kinase inhibitors. Cancer Res. 2018;78(4):1044–1057. doi:10.1158/0008-5472.CAN-17-1904
  • Tatsumi K, Sou YS, Tada N, et al. A novel type of E3 ligase for the Ufm1 conjugation system. J Biol Chem. 2010;285(8):5417–5427. doi:10.1074/jbc.M109.036814
  • Wei Y, Xu X. UFMylation: a Unique & Fashionable Modification for Life. Genomics, Proteomics Bioinforma. 2016;14(3):140–146. doi:10.1016/j.gpb.2016.04.001
  • Naidoo J, Sima CS, Rodriguez K, et al. Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: clinical outcomes and response to erlotinib. Cancer. 2015;121(18):3212–3220. doi:10.1002/cncr.29493
  • Beau-Faller M, Prim N, Ruppert A-M-M, et al. Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol. 2013;25(1):126–131. doi:10.1093/annonc/mdt418
  • Yang JCH, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): Analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. doi:10.1016/S1470-2045(14)71173-8
  • Sequist LV, Besse B, Lynch TJ, et al. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(18):3076–3083. doi:10.1200/JCO.2009.27.9414
  • Kim TM, Ock C-Y, Kim M, et al. Phase II study of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation: a multicenter trial of the Korean Cancer Study Group (LU17-19). Ann Oncol. 2019;30:v628. doi:10.1093/annonc/mdz260.051
  • Fang W, Huang Y, Hong S, et al. EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer. BMC Cancer. 2019;19(1):1–9. doi:10.1186/s12885-019-5820-0