Osimertinib Induces the Opposite Effect of Proliferation and Migration in the Drug Resistance of EGFR-T790M Non-small Cell Lung Cancer Cells


Cite item

Full Text

Abstract

Background: Lung cancer has become one of the leading causes of cancer incidence and mortality worldwide. Non-small cell lung carcinoma (NSCLC) is the most common type among all lung cancer cases. NSCLC patients contained high levels of activating epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion, L858R and T790M. Osimertinib, a third-generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), has therapeutic efficacy on the EGFR-T790M mutation of NSCLC patients; however, treatment of osimertinib still can induce drug resistance in lung cancer patients. Therefore, investigation of the drug resistance mechanisms of osimertinib will provide novel strategies for lung cancer therapy.

Methods: The H1975OR osimertinib-resistant cell line was established by prolonged exposure with osimertinib derived from the H1975 cells. The cell proliferation ability was evaluated by the cell viability and cell growth assays. The cell migration ability was determined by the Boyden chamber assays. The differential gene expression profile was analyzed by genome-wide RNA sequencing. The protein expression and location were analyzed by western blot and confocal microscopy.

Results: In this study, we established the osimertinib-resistant H1975 (T790M/L858R) cancer cells, named the H1975OR cell line. The cell growth ability was decreased in the H1975OR cells by comparison with the H1975 parental cells. Conversely, the cell migration ability was elevated in the H1975OR cells. We found the differential gene expression profile of cell proliferation and migration pathways between the H1975OR and H1975 parental cells. Interestingly, the protein levels of phospho-EGFR, PD-L1, E-cadherin and β-catenin were decreased, but the survivin and N-cadherin proteins were increased in the H1975OR drug-resistant cells.

Conclusion: Osimertinib induces the opposite effect of proliferation and migration in the drug resistance of EGFRT790M lung cancer cells. We suggest that differential gene and protein expressions in the cell proliferation and migration pathways may mediate the drug resistance of osimertinib in lung cancer cells. Understanding the molecular drugresistant mechanisms of proliferation and migration pathways of osimertinib may provide novel targets and strategies for the clinical treatment of EGFR-TKIs in lung cancer patients.

About the authors

Rou-Hsin Wang

InInstitute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University

Email: info@benthamscience.net

Chien-Jen Chang

Department of Biological Science and Technology, National Yang Ming Chiao Tung University

Email: info@benthamscience.net

Chien-Hung Chen

Department of Biological Science and Technology, National Yang Ming Chiao Tung University

Email: info@benthamscience.net

Kuang-Kai Liu

Department of Biological Science and Technology, National Yang Ming Chiao Tung University

Email: info@benthamscience.net

Jui-I Chao

Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin., 2022, 72(1), 7-33. doi: 10.3322/caac.21708 PMID: 35020204
  2. Herbst, R.S.; Heymach, J.V.; Lippman, S.M. Lung Cancer. N. Engl. J. Med., 2008, 359(13), 1367-1380. doi: 10.1056/NEJMra0802714 PMID: 18815398
  3. Sabbula, B.R.; Anjum, F. Squamous Cell Lung Cancer; StatPearls: Treasure Island, FL, 2022.
  4. Bethune, G.; Bethune, D.; Ridgway, N.; Xu, Z. Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. J. Thorac. Dis., 2010, 2(1), 48-51. PMID: 22263017
  5. Kanthala, S.; Pallerla, S.; Jois, S. Current and future targeted therapies for non-small-cell lung cancers with aberrant EGF receptors. Future Oncol., 2015, 11(5), 865-878. doi: 10.2217/fon.14.312 PMID: 25757687
  6. Hubbard, S.R.; Miller, W.T. Receptor tyrosine kinases: Mechanisms of activation and signaling. Curr. Opin. Cell Biol., 2007, 19(2), 117-123. doi: 10.1016/j.ceb.2007.02.010 PMID: 17306972
  7. Marshall, C.J. Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell, 1995, 80(2), 179-185. doi: 10.1016/0092-8674(95)90401-8 PMID: 7834738
  8. Ding, L.; Getz, G.; Wheeler, D.A.; Mardis, E.R.; McLellan, M.D.; Cibulskis, K.; Sougnez, C.; Greulich, H.; Muzny, D.M.; Morgan, M.B.; Fulton, L.; Fulton, R.S.; Zhang, Q.; Wendl, M.C.; Lawrence, M.S.; Larson, D.E.; Chen, K.; Dooling, D.J.; Sabo, A.; Hawes, A.C.; Shen, H.; Jhangiani, S.N.; Lewis, L.R.; Hall, O.; Zhu, Y.; Mathew, T.; Ren, Y.; Yao, J.; Scherer, S.E.; Clerc, K.; Metcalf, G.A.; Ng, B.; Milosavljevic, A.; Gonzalez-Garay, M.L.; Osborne, J.R.; Meyer, R.; Shi, X.; Tang, Y.; Koboldt, D.C.; Lin, L.; Abbott, R.; Miner, T.L.; Pohl, C.; Fewell, G.; Haipek, C.; Schmidt, H.; Dunford-Shore, B.H.; Kraja, A.; Crosby, S.D.; Sawyer, C.S.; Vickery, T.; Sander, S.; Robinson, J.; Winckler, W.; Baldwin, J.; Chirieac, L.R.; Dutt, A.; Fennell, T.; Hanna, M.; Johnson, B.E.; Onofrio, R.C.; Thomas, R.K.; Tonon, G.; Weir, B.A.; Zhao, X.; Ziaugra, L.; Zody, M.C.; Giordano, T.; Orringer, M.B.; Roth, J.A.; Spitz, M.R.; Wistuba, I.I., II; Ozenberger, B.; Good, P.J.; Chang, A.C.; Beer, D.G.; Watson, M.A.; Ladanyi, M.; Broderick, S.; Yoshizawa, A.; Travis, W.D.; Pao, W.; Province, M.A.; Weinstock, G.M.; Varmus, H.E.; Gabriel, S.B.; Lander, E.S.; Gibbs, R.A.; Meyerson, M.; Wilson, R.K. Somatic mutations affect key pathways in lung adenocarcinoma. Nature, 2008, 455(7216), 1069-1075. doi: 10.1038/nature07423 PMID: 18948947
  9. Tomas, A.; Futter, C.E.; Eden, E.R. EGF receptor trafficking: Consequences for signaling and cancer. Trends Cell Biol., 2014, 24(1), 26-34. doi: 10.1016/j.tcb.2013.11.002 PMID: 24295852
  10. Mao, H.; Sun, Y. Neddylation-independent activities of MLN4924. Adv. Exp. Med. Biol., 2020, 1217, 363-372. doi: 10.1007/978-981-15-1025-0_21 PMID: 31898238
  11. Brückl, W.; Tufman, A.; Huber, R.M. Advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations: First-line treatment with afatinib and other EGFR TKIs. Expert Rev. Anticancer Ther., 2017, 17(2), 143-155. doi: 10.1080/14737140.2017.1266265 PMID: 27898252
  12. Harrison, P.T.; Vyse, S.; Huang, P.H. 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 PMID: 31562956
  13. Seshacharyulu, P.; Ponnusamy, M.P.; Haridas, D.; Jain, M.; Ganti, A.K.; Batra, S.K. Targeting the EGFR signaling pathway in cancer thera-py. Expert Opin. Ther. Targets, 2012, 16(1), 15-31. doi: 10.1517/14728222.2011.648617 PMID: 22239438
  14. Sullivan, I.; Planchard, D. Next-generation EGFR tyrosine kinase inhibitors for treating EGFR-mutant lung cancer beyond first line. Front. Med., 2017, 3, 76. doi: 10.3389/fmed.2016.00076 PMID: 28149837
  15. Lin, Y.; Wang, X.; Jin, H. EGFR-TKI resistance in NSCLC patients: Mechanisms and strategies. Am. J. Cancer Res., 2014, 4(5), 411-435. PMID: 25232485
  16. Wang, Y.; Guo, Z.; Li, Y.; Zhou, Q. Development of epidermal growth factor receptor tyrosine kinase inhibitors against EGFR T790M. Mutation in non small-cell lung carcinoma. Open Med., 2016, 11(1), 68-77. doi: 10.1515/med-2016-0014 PMID: 28352770
  17. Choi, Y.W.; Choi, J.H. Does the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor differ according to the type of EGFR mutation in non-small cell lung cancer? Korean J. Intern. Med., 2017, 32(3), 422-428. doi: 10.3904/kjim.2016.190 PMID: 28352061
  18. Gao, X.; Le, X.; Costa, D.B. The safety and efficacy of osimertinib for the treatment of EGFR T790M mutation positive non-small-cell lung cancer. Exp. Rev. Anticancer Ther., 2016, 16(4), 383-390. doi: 10.1586/14737140.2016.1162103 PMID: 26943236
  19. Duggirala, K.B.; Lee, Y.; Lee, K. Chronicles of EGFR Tyrosine Kinase Inhibitors: Targeting EGFR C797S containing triple mutations. Biomol. Ther., 2022, 30(1), 19-27. doi: 10.4062/biomolther.2021.047 PMID: 34074804
  20. Liang, H.; Pan, Z.; Wang, W.; Guo, C.; Chen, D.; Zhang, J.; Zhang, Y.; Tang, S.; He, J.; Liang, W. The alteration of T790M between 19 del and L858R in NSCLC in the course of EGFR-TKIs therapy: A literature-based pooled analysis. J. Thorac. Dis., 2018, 10(4), 2311-2320. doi: 10.21037/jtd.2018.03.150 PMID: 29850136
  21. Cross, D.A.E.; Ashton, S.E.; Ghiorghiu, S.; Eberlein, C.; Nebhan, C.A.; Spitzler, P.J.; Orme, J.P.; Finlay, M.R.V.; Ward, R.A.; Mellor, M.J.; Hughes, G.; Rahi, A.; Jacobs, V.N.; Brewer, M.R.; Ichihara, E.; Sun, J.; Jin, H.; Ballard, P.; Al-Kadhimi, K.; Rowlinson, R.; Klinowska, T.; Richmond, G.H.P.; Cantarini, M.; Kim, D.W.; Ranson, M.R.; Pao, W. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov., 2014, 4(9), 1046-1061. doi: 10.1158/2159-8290.CD-14-0337 PMID: 24893891
  22. Masuzawa, K.; Yasuda, H.; Hamamoto, J.; Nukaga, S.; Hirano, T.; Kawada, I.; Naoki, K.; Soejima, K.; Betsuyaku, T. Characterization of the efficacies of osimertinib and nazartinib against cells expressing clinically relevant epidermal growth factor receptor mutations. Oncotarget, 2017, 8(62), 105479-105491. doi: 10.18632/oncotarget.22297 PMID: 29285266
  23. Igawa, S.; Ono, T.; Kasajima, M.; Ishihara, M.; Hiyoshi, Y.; Kusuhara, S.; Nishinarita, N.; Fukui, T.; Kubota, M.; Sasaki, J.; Hisashi, M.; Yokoba, M.; Katagiri, M.; Naoki, K. Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: A prospective observational study. Cancer Manag. Res., 2019, 11, 4883-4892. doi: 10.2147/CMAR.S207170 PMID: 31213907
  24. Ito, K.; Hataji, O. Osimertinib therapy as first-line treatment before acquiring T790M mutation: From AURA1 trial. J. Thorac. Dis., 2018, 10(S26), S3071-S3077. doi: 10.21037/jtd.2018.07.52 PMID: 30430025
  25. Mancini, M.; Gal, H.; Gaborit, N.; Mazzeo, L.; Romaniello, D.; Salame, T.M.; Lindzen, M.; Mahlknecht, G.; Enuka, Y.; Burton, D.G.; Roth, L.; Noronha, A.; Marrocco, I.; Adreka, D.; Altstadter, R.E.; Bousquet, E.; Downward, J.; Maraver, A.; Krizhanovsky, V.; Yarden, Y. An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors. EMBO Mol. Med., 2018, 10(2), 294-308. PMID: 29212784
  26. Ma, L.; Chen, R.; Wang, F.; Ma, L.L.; Yuan, M.M.; Chen, R.R.; Liu, J. EGFR L718Q mutation occurs without T790M mutation in a lung adenocarcinoma patient with acquired resistance to osimertinib. Ann. Transl. Med., 2019, 7(9), 207. doi: 10.21037/atm.2019.04.37 PMID: 31205925
  27. Tang, Z.H.; Lu, J.J. Osimertinib resistance in non-small cell lung cancer: Mechanisms and therapeutic strategies. Cancer Lett., 2018, 420, 242-246. doi: 10.1016/j.canlet.2018.02.004 PMID: 29425688
  28. Tan, C.S.; Kumarakulasinghe, N.B.; Huang, Y.Q.; Ang, Y.L.E.; Choo, J.R.E.; Goh, B.C.; Soo, R.A. Third generation EGFR TKIs: Current data and future directions. Mol. Cancer, 2018, 17(1), 29. doi: 10.1186/s12943-018-0778-0 PMID: 29455654
  29. Lawson, C.D.; Ridley, A.J. Rho GTPase signaling complexes in cell migration and invasion. J. Cell Biol., 2018, 217(2), 447-457. doi: 10.1083/jcb.201612069 PMID: 29233866
  30. Sakumura, Y.; Tsukada, Y.; Yamamoto, N.; Ishii, S. A molecular model for axon guidance based on cross talk between rho GTPases. Biophys. J., 2005, 89(2), 812-822. doi: 10.1529/biophysj.104.055624 PMID: 15923236
  31. Liu, M.; Bi, F.; Zhou, X.; Zheng, Y. Rho GTPase regulation by miRNAs and covalent modifications. Trends Cell Biol., 2012, 22(7), 365-373. doi: 10.1016/j.tcb.2012.04.004 PMID: 22572609
  32. Iderzorig, T.; Kellen, J.; Osude, C.; Singh, S.; Woodman, J.A.; Garcia, C.; Puri, N. Comparison of epithelial mesenchymal transition medi-ated tyrosine kinase inhibitor resistance in non-small cell lung cancer cell lines with wild type EGFR and mutant type EGFR. Biochem. Biophys. Res. Commun., 2018, 496(2), 770-777.
  33. Du, W.; Liu, X.; Fan, G.; Zhao, X.; Sun, Y.; Wang, T.; Zhao, R.; Wang, G.; Zhao, C.; Zhu, Y.; Ye, F.; Jin, X.; Zhang, F.; Zhong, Z.; Li, X. From cell membrane to the nucleus: An emerging role of E‐cadherin in gene transcriptional regulation. J. Cell. Mol. Med., 2014, 18(9), 1712-1719. doi: 10.1111/jcmm.12340 PMID: 25164084
  34. Sasaki, C.Y.; Lin, H.; Passaniti, A. Expression of E-cadherin reduces Bcl-2 expression and increases sensitivity to etoposide-induced apoptosis. Int. J. Cancer, 2000, 86(5), 660-666. doi: 10.1002/(SICI)1097-0215(20000601)86:5<660:AID-IJC9>3.0.CO;2-X PMID: 10797287
  35. Liu, K.; Chen, X.; Wu, L.; Chen, S.; Fang, N.; Cai, L.; Jia, J. ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial-mesenchymal transition. BMC Pulm. Med., 2021, 21(1), 163. doi: 10.1186/s12890-021-01540-4 PMID: 33992097
  36. Liu, Z.; Gao, W. Overcoming acquired resistance of gefitinib in lung cancer cells without T790M by AZD9291 or Twist1 knockdown in vitro and in vivo. Arch. Toxicol., 2019, 93(6), 1555-1571. doi: 10.1007/s00204-019-02453-2 PMID: 30993382
  37. Jiang, X.M.; Xu, Y.L.; Huang, M.Y.; Zhang, L.L.; Su, M.X.; Chen, X.; Lu, J.J. Osimertinib (AZD9291) decreases programmed death lig-and-1 in EGFR-mutated non-small cell lung cancer cells. Acta Pharmacol. Sin., 2017, 38(11), 1512-1520. doi: 10.1038/aps.2017.123 PMID: 28880013
  38. Huang, M.Y.; Jiang, X.M.; Wang, B.L.; Sun, Y.; Lu, J.J. Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: Strategies and mechanisms. Pharmacol. Ther., 2021, 219107694 doi: 10.1016/j.pharmthera.2020.107694 PMID: 32980443
  39. Wang, S.P.; Hsu, Y.P.; Chang, C.J.; Chan, Y.C.; Chen, C.H.; Wang, R.H.; Liu, K.K.; Pan, P.Y.; Wu, Y.H.; Yang, C.M.; Chen, C.; Yang, J.M.; Liang, M.C.; Wong, K.K.; Chao, J.I. A novel EGFR inhibitor suppresses survivin expression and tumor growth in human gefitinib-resistant EGFR-wild type and -T790M non-small cell lung cancer. Biochem. Pharmacol., 2021, 193114792 doi: 10.1016/j.bcp.2021.114792
  40. Head, S.R.; Komori, H.K.; LaMere, S.A.; Whisenant, T.; Van Nieuwerburgh, F.; Salomon, D.R.; Ordoukhanian, P. Library construction for next-generation sequencing: Overviews and challenges. Biotechniques, 2014, 56(2), 61-77. doi: 10.2144/000114133 PMID: 24502796
  41. Gillespie, M.; Jassal, B.; Stephan, R.; Milacic, M.; Rothfels, K.; Senff-Ribeiro, A.; Griss, J.; Sevilla, C.; Matthews, L.; Gong, C.; Deng, C.; Varusai, T.; Ragueneau, E.; Haider, Y.; May, B.; Shamovsky, V.; Weiser, J.; Brunson, T.; Sanati, N.; Beckman, L.; Shao, X.; Fabregat, A.; Sidiropoulos, K.; Murillo, J.; Viteri, G.; Cook, J.; Shorser, S.; Bader, G.; Demir, E.; Sander, C.; Haw, R.; Wu, G.; Stein, L.; Hermjakob, H.; D'Eustachio, P. The reactome pathway knowledgebase 2022. Nucleic Acids Res., 2022, 50(D1), D687-D692. doi: 10.1093/nar/gkab1028 PMID: 34788843
  42. Kanehisa, M.; Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 2000, 28(1), 27-30. doi: 10.1093/nar/28.1.27 PMID: 10592173
  43. Subramanian, A.; Tamayo, P.; Mootha, V.K.; Mukherjee, S.; Ebert, B.L.; Gillette, M.A.; Paulovich, A.; Pomeroy, S.L.; Golub, T.R.; Lander, E.S.; Mesirov, J.P. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA, 2005, 102(43), 15545-15550. doi: 10.1073/pnas.0506580102 PMID: 16199517
  44. Sah, N.K.; Khan, Z.; Khan, G.J.; Bisen, P.S. Structural, functional and therapeutic biology of survivin. Cancer Lett., 2006, 244(2), 164-171. doi: 10.1016/j.canlet.2006.03.007 PMID: 16621243
  45. Chen, X.; Duan, N.; Zhang, C.; Zhang, W. Survivin and tumorigenesis: Molecular mechanisms and therapeutic strategies. J. Cancer, 2016, 7(3), 314-323. doi: 10.7150/jca.13332 PMID: 26918045
  46. Chandele, A.; Prasad, V.; Jagtap, J.C.; Shukla, R.; Shastry, P.R. Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis. Neoplasia, 2004, 6(1), 29-40. doi: 10.1016/S1476-5586(04)80051-4 PMID: 15068669
  47. Cheng, F.; Eriksson, J.E. Intermediate filaments and the regulation of cell motility during regeneration and wound healing. Cold Spring Harb. Perspect. Biol., 2017, 9(9)a022046 doi: 10.1101/cshperspect.a022046 PMID: 28864602
  48. Gao, Y.; Nihira, N.T.; Bu, X.; Chu, C.; Zhang, J.; Kolodziejczyk, A.; Fan, Y.; Chan, N.T.; Ma, L.; Liu, J.; Wang, D.; Dai, X.; Liu, H.; Ono, M.; Nakanishi, A.; Inuzuka, H.; North, B.J.; Huang, Y.H.; Sharma, S.; Geng, Y.; Xu, W.; Liu, X.S.; Li, L.; Miki, Y.; Sicinski, P.; Freeman, G.J.; Wei, W. Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nat. Cell Biol., 2020, 22(9), 1064-1075. doi: 10.1038/s41556-020-0562-4 PMID: 32839551
  49. Lee, H.H.; Wang, Y.N.; Xia, W.; Chen, C.H.; Rau, K.M.; Ye, L.; Wei, Y.; Chou, C.K.; Wang, S.C.; Yan, M.; Tu, C.Y.; Hsia, T.C.; Chiang, S.F.; Chao, K.S.C.; Wistuba, I.I., II; Hsu, J.L.; Hortobagyi, G.N.; Hung, M.C. Removal of N-linked glycosylation enhances PD-L1 detec-tion and predicts anti-PD-1/PD-L1 therapeutic efficacy. Cancer Cell, 2019, 36(2), 168-178. doi: 10.1016/j.ccell.2019.06.008 PMID: 31327656
  50. Yu, J.; Qin, B.; Moyer, A.M.; Nowsheen, S.; Tu, X.; Dong, H.; Boughey, J.C.; Goetz, M.P.; Weinshilboum, R.; Lou, Z.; Wang, L. Regula-tion of sister chromatid cohesion by nuclear PD-L1. Cell Res., 2020, 30(7), 590-601. doi: 10.1038/s41422-020-0315-8 PMID: 32350394
  51. Kornepati, A.V.R.; Vadlamudi, R.K.; Curiel, T.J. Programmed death ligand 1 signals in cancer cells. Nat. Rev. Cancer, 2022, 22(3), 174-189. doi: 10.1038/s41568-021-00431-4 PMID: 35031777
  52. 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. doi: 10.1038/s41416-019-0573-8 PMID: 31564718
  53. Chiu, S.J.; Hsu, T.S.; Chao, J.I. Opposing securin and p53 protein expression in the oxaliplatin-induced cytotoxicity of human colorectal cancer cells. Toxicol. Lett., 2006, 167(2), 122-130. doi: 10.1016/j.toxlet.2006.08.018 PMID: 17045763
  54. Chao, J.I.; Hsu, S.H.; Tsou, T.C. Depletion of securin increases arsenite-induced chromosome instability and apoptosis via a p53-independent pathway. Toxicol. Sci., 2006, 90(1), 73-86. doi: 10.1093/toxsci/kfj070 PMID: 16338954
  55. Liu, H.F.; Hsiao, P.W.; Chao, J.I. Celecoxib induces p53-PUMA pathway for apoptosis in human colorectal cancer cells. Chem. Biol. Interact., 2008, 176(1), 48-57. doi: 10.1016/j.cbi.2008.07.012 PMID: 18760266
  56. La Monica, S.; Fumarola, C.; Cretella, D.; Bonelli, M.; Minari, R.; Cavazzoni, A.; Digiacomo, G.; Galetti, M.; Volta, F.; Mancini, M.; Petro-nini, P.G.; Tiseo, M.; Alfieri, R. Efficacy of the CDK4/6 dual inhibitor abemaciclib in EGFR-mutated NSCLC cell lines with different re-sistance mechanisms to osimertinib. Cancers, 2020, 13(1), 6. doi: 10.3390/cancers13010006 PMID: 33374971
  57. Qin, Q.; Li, X.; Liang, X.; Zeng, L.; Wang, J.; Sun, L.; Zhong, D. CDK4/6 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 PMID: 32677256
  58. Della Corte, C.M.; Malapelle, U.; Vigliar, E.; Pepe, F.; Troncone, G.; Ciaramella, V.; Troiani, T.; Martinelli, E.; Belli, V.; Ciardiello, F.; Morgillo, F. Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired resistance in human lung cancer cells with activating mutation of EGFR. Oncotarget, 2017, 8(14), 23020-23032. doi: 10.18632/oncotarget.15479 PMID: 28416737
  59. Zhang, K.; Li, Y.; Liu, W.; Gao, X.; Zhang, K. Silencing survivin expression inhibits the tumor growth of non-small-cell lung cancer cells in vitro and in vivo. Mol. Med. Rep., 2015, 11(1), 639-644. doi: 10.3892/mmr.2014.2729 PMID: 25333812
  60. Lou, Y.; Diao, L.; Cuentas, E.R.P.; Denning, W.L.; Chen, L.; Fan, Y.H.; Byers, L.A.; Wang, J.; Papadimitrakopoulou, V.A.; Behrens, C.; Rodriguez, J.C.; Hwu, P.; Wistuba, I.I.; Heymach, J.V.; Gibbons, D.L. Epithelial-mesenchymal transition is associated with a distinct tu-mor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma. Clin. Cancer Res., 2016, 22(14), 3630-3642. doi: 10.1158/1078-0432.CCR-15-1434 PMID: 26851185
  61. Jiang, Y.; Zhan, H. Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion. Cancer Lett., 2020, 468, 72-81. doi: 10.1016/j.canlet.2019.10.013 PMID: 31605776

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2023 Bentham Science Publishers