284
Views
3
CrossRef citations to date
0
Altmetric
Research Article

EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools

, , , , ORCID Icon, & ORCID Icon show all
Pages 9808-9827 | Received 05 Aug 2022, Accepted 07 Nov 2022, Published online: 16 Dec 2022

References

  • Afgan, E., Baker, D., Batut, B., van den Beek, M., Bouvier, D., Cech, M., Chilton, J., Clements, D., Coraor, N., Grüning, B. A., Guerler, A., Hillman-Jackson, J., Hiltemann, S., Jalili, V., Rasche, H., Soranzo, N., Goecks, J., Taylor, J., Nekrutenko, A., & Blankenberg, D. (2018). The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Research, 46(W1), W537–W544. https://doi.org/10.1093/nar/gky379
  • Aisner, D. L., Sholl, L. M., Berry, L. D., Rossi, M. R., Chen, H., Fujimoto, J., Moreira, A. L., Ramalingam, S. S., Villaruz, L. C., Otterson, G. A., Haura, E., Politi, K., Glisson, B., Cetnar, J., Garon, E. B., Schiller, J., Waqar, S. N., Sequist, L. V., Brahmer, J., … Kwiatkowski, D. J., LCMC2 Investigators. (2018). The impact of smoking and TP53 Mutations in lung adenocarcinoma patients with targetable mutations-the Lung Cancer Mutation Consortium (LCMC2). Clinical Cancer Research, 24(5), 1038–1047. https://doi.org/10.1158/1078-0432.CCR-17-2289
  • Aliperti, L. A., Predina, J. D., Vachani, A., & Singhal, S. (2011). Local and systemic recurrence is the Achilles heel of cancer surgery. Annals of Surgical Oncology, 18(3), 603–607. https://doi.org/10.1245/s10434-010-1442-0
  • Allison, M. (2010). Turning the tide in lung cancer. Nature Biotechnology, 28(10), 999–1002. https://doi.org/10.1038/nbt1010-999
  • American Cancer Society. (2022). Cancer Facts and Figures 2022.
  • Andrews, S. (2010). FastQC A quality control tool for high throughput sequence data.
  • Babicki, S., Arndt, D., Marcu, A., Liang, Y., Grant, J. R., Maciejewski, A., & Wishart, D. S. (2016). Heatmapper: Web-enabled heat mapping for all. Nucleic Acids Research, 44(W1), W147–W153. https://doi.org/10.1093/nar/gkw419
  • Bai, X.-Y., Zhang, X.-C., Yang, S.-Q., An, S.-J., Chen, Z.-H., Su, J., Xie, Z., Gou, L.-Y., & Wu, Y.-L. (2016). Blockade of hedgehog signaling synergistically increases sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer cell lines. PLoS One, 11(3), e0149370. https://doi.org/10.1371/journal.pone.0149370
  • Barrett, T., Wilhite, S. E., Ledoux, P., Evangelista, C., Kim, I. F., Tomashevsky, M., Marshall, K. A., Phillippy, K. H., Sherman, P. M., Holko, M., Yefanov, A., Lee, H., Zhang, N., Robertson, CL., Serova, N., Davis, S., & Soboleva, A. (2013). NCBI GEO: Archive for functional genomics data sets–update. Nucleic acids research, 41(Database issue), D991–5. https://doi.org/10.1093/nar/gks1193.
  • Bhang, H-e. C., Ruddy, D. A., Krishnamurthy Radhakrishna, V., Caushi, J. X., Zhao, R., Hims, M. M., Singh, A. P., Kao, I., Rakiec, D., Shaw, P., Balak, M., Raza, A., Ackley, E., Keen, N., Schlabach, M. R., Palmer, M., Leary, R. J., Chiang, D. Y., Sellers, W. R., … Stegmeier, F. (2015). Studying clonal dynamics in response to cancer therapy using high-complexity barcoding. Nature Medicine, 21(5), 440–448. https://doi.org/10.1038/nm.3841
  • Bhullar, K. S., Lagarón, N. O., McGowan, E. M., Parmar, I., Jha, A., Hubbard, B. P., & Rupasinghe, H. P. V. (2018). Kinase-targeted cancer therapies: Progress, challenges and future directions. Molecular Cancer, 17(1), 48. https://doi.org/10.1186/s12943-018-0804-2
  • Blackledge, G., Averbuch, S., Kay, A., & Barton, J. (2000). Anti-EGF receptor therapy. Prostate Cancer and Prostatic Diseases, 3(4), 296–302. https://doi.org/10.1038/sj.pcan.4500488
  • Blakely, C. M., & Bivona, T. G. (2012). Resiliency of lung cancers to EGFR inhibitor treatment unveiled, offering opportunities to divide and conquer EGFR inhibitor resistance. Cancer Discovery, 2(10), 872–875. https://doi.org/10.1158/2159-8290.CD-12-0387
  • Blakely, C. M., Pazarentzos, E., Olivas, V., Asthana, S., Yan, J. J., Tan, I., Hrustanovic, G., Chan, E., Lin, L., Neel, D. S., Newton, W., Bobb, K. L., Fouts, T. R., Meshulam, J., Gubens, M. A., Jablons, D. M., Johnson, J. R., Bandyopadhyay, S., Krogan, N. J., & Bivona, T. G. (2015). NF-kappaB-activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer. Cell Reports, 11(1), 98–110. https://doi.org/10.1016/j.celrep.2015.03.012
  • Bolger, A. M., Lohse, M., & Usadel, B. (2014). Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics (Oxford, England), 30(15), 2114–2120. https://doi.org/10.1093/bioinformatics/btu170
  • Brady, S. W., Zhang, J., Seok, D., Wang, H., & Yu, D. (2014). Enhanced PI3K p110alpha signaling confers acquired lapatinib resistance that can be effectively reversed by a p110alpha-selective PI3K inhibitor. Molecular Cancer Therapeutics, 13(1), 60–70. https://doi.org/10.1158/1535-7163.MCT-13-0518
  • Caiazza, F., McCarthy, N. S., Young, L., Hill, A. D. K., Harvey, B. J., & Thomas, W. (2011). Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours. British Journal of Cancer, 104(2), 338–344. https://doi.org/10.1038/sj.bjc.6606025
  • Casás-Selves, M., Kim, J., Zhang, Z., Helfrich, B. A., Gao, D., Porter, C. C., Scarborough, H. A., Bunn, P. A., Chan, D. C., Tan, A. C., & DeGregori, J. (2012). Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Research, 72(16), 4154–4164. https://doi.org/10.1158/0008-5472.CAN-11-2848
  • Cheng, S.-C., Quintin, J., Cramer, R. A., Shepardson, K. M., Saeed, S., Kumar, V., Giamarellos-Bourboulis, E. J., Martens, J. H. A., Rao, N. A., Aghajanirefah, A., Manjeri, G. R., Li, Y., Ifrim, D. C., Arts, R. J. W., van der Veer, B. M. J. W., Deen, P. M. T., Logie, C., O'Neill, L. A., Willems, P., … Netea, M. G. (2014). mTOR- and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity. Science (New York, N.Y.), 345(6204), 1250684.
  • Chesnokova, L. S., & Yurochko, A. D. (2021). Using a phosphoproteomic screen to profile early changes during HCMV infection of human monocytes. Methods in Molecular Biology (Clifton, N.J.), 2244, 233–246.
  • Chiang, C.-T., Demetriou, A. N., Ung, N., Choudhury, N., Ghaffarian, K., Ruderman, D. L., & Mumenthaler, S. M. (2018). mTORC2 contributes to the metabolic reprogramming in EGFR tyrosine-kinase inhibitor resistant cells in non-small cell lung cancer. Cancer Letters, 434, 152–159. https://doi.org/10.1016/j.canlet.2018.07.025
  • Cipriano, R., Bryson, B. L., Miskimen, K. L. S., Bartel, C. A., Hernandez-Sanchez, W., Bruntz, R. C., Scott, S. A., Lindsley, C. W., Brown, H. A., & Jackson, M. W. (2014). Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B. Oncogene, 33(25), 3298–3306. https://doi.org/10.1038/onc.2013.293
  • Coelho Ribeiro, M. d. L., Espinosa, J., Islam, S., Martinez, O., Thanki, J. J., Mazariegos, S., Nguyen, T., Larina, M., Xue, B., & Uversky, V. N. (2013). Malleable ribonucleoprotein machine: Protein intrinsic disorder in the Saccharomyces cerevisiae spliceosome. PeerJ, 1, e2. https://doi.org/10.7717/peerj.2
  • de Fijter, J. W. (2017). Cancer and mTOR Inhibitors in Transplant Recipients. Transplantation, 101(1), 45–55. https://doi.org/10.1097/TP.0000000000001447
  • De Rosa, V., Iommelli, F., Monti, M., Fonti, R., Votta, G., Stoppelli, M. P., & Del Vecchio, S. (2015). Reversal of warburg effect and reactivation of oxidative phosphorylation by differential inhibition of EGFR signaling pathways in non-small cell lung cancer. Clinical Cancer Research, 21(22), 5110–5120. https://doi.org/10.1158/1078-0432.CCR-15-0375
  • Ding, C.-B., Yu, W.-N., Feng, J.-H., & Luo, J.-M. (2015). Structure and function of Gab2 and its role in cancer (Review). Molecular Medicine Reports, 12(3), 4007–4014. https://doi.org/10.3892/mmr.2015.3951
  • Dong, Z., Meller, J., Succop, P., Wang, J., Wikenheiser-Brokamp, K., Starnes, S., & Lu, S. (2014). Secretory phospholipase A2-IIa upregulates HER/HER2-elicited signaling in lung cancer cells. International Journal of Oncology, 45(3), 978–984. https://doi.org/10.3892/ijo.2014.2486
  • Doroshow, D. B., & Herbst, R. S. (2018). Treatment of advanced non-small cell lung cancer in 2018. JAMA Oncology, 4(4), 569–570. https://doi.org/10.1001/jamaoncol.2017.5190
  • Dosztányi, Z., Csizmok, V., Tompa, P., & Simon, I. (2005). IUPred: Web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics (Oxford, England), 21(16), 3433–3434.
  • Dosztanyi, Z., et al. (2005). The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins. Journal of Molecular Biology, 347(4), 827–839.
  • Douillard, J.-Y., Ostoros, G., Cobo, M., Ciuleanu, T., McCormack, R., Webster, A., & Milenkova, T. (2014). First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: A phase-IV, open-label, single-arm study. British Journal of Cancer, 110(1), 55–62. https://doi.org/10.1038/bjc.2013.721
  • Du, X., Yang, B., An, Q., Assaraf, Y. G., Cao, X., & Xia, J. (2021). Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors. Innovation (Cambridge (MA)), 2(2), 100103. https://doi.org/10.1016/j.xinn.2021.100103
  • Economopoulou, P., & Mountzios, G. (2018). The emerging treatment landscape of advanced non-small cell lung cancer. Annals of Translational Medicine, 6(8), 138. https://doi.org/10.21037/atm.2017.11.07
  • Fedor, D., Johnson, W. R., & Singhal, S. (2013). Local recurrence following lung cancer surgery: Incidence, risk factors, and outcomes. Surgical Oncology, 22(3), 156–161. https://doi.org/10.1016/j.suronc.2013.04.002
  • Goetzman, E. S., & Prochownik, E. V. (2018). The role for Myc in coordinating glycolysis, oxidative phosphorylation, glutaminolysis, and fatty acid metabolism in normal and neoplastic tissues. Front Endocrinol (Lausanne), 9, 129.
  • Gringeri, E., Carraro, A., Tibaldi, E., D'Amico, F. E., Mancon, M., Toninello, A., Pagano, M. A., Vio, C., Cillo, U., & Brunati, A. M. (2009). Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration. The Biochemical Journal, 425(2), 401–412. https://doi.org/10.1042/BJ20090902
  • Han, W., & Lo, H. W. (2012). Landscape of EGFR signaling network in human cancers: Biology and therapeutic response in relation to receptor subcellular locations. Cancer Letters, 318(2), 124–134. https://doi.org/10.1016/j.canlet.2012.01.011
  • Hata, A. N., Niederst, M. J., Archibald, H. L., Gomez-Caraballo, M., Siddiqui, F. M., Mulvey, H. E., Maruvka, Y. E., Ji, F., Bhang, H-e. C., Krishnamurthy Radhakrishna, V., Siravegna, G., Hu, H., Raoof, S., Lockerman, E., Kalsy, A., Lee, D., Keating, C. L., Ruddy, D. A., Damon, L. J., … Engelman, J. A. (2016). Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nature Medicine, 22(3), 262–269. https://doi.org/10.1038/nm.4040
  • He, B., Wang, K., Liu, Y., Xue, B., Uversky, V. N., & Dunker, A. K. (2009). Predicting intrinsic disorder in proteins: An overview. Cell Research, 19(8), 929–949. https://doi.org/10.1038/cr.2009.87
  • He, J., Huang, Z., Han, L., Gong, Y., & Xie, C. (2021). Mechanisms and management of 3rdgeneration EGFRTKI resistance in advanced nonsmall cell lung cancer. International Journal of Oncology, 59(5). https://doi.org/10.3892/ijo.2021.5270
  • Hirsh, V. (2011). Afatinib (BIBW 2992) development in non-small-cell lung cancer. Future Oncology (London, England), 7(7), 817–825. https://doi.org/10.2217/fon.11.62
  • Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S. (2014). Drug resistance in cancer: An overview. Cancers (Basel), 6(3), 1769–1792. https://doi.org/10.3390/cancers6031769
  • Howell, M. C., G, R., Khalil, R., Foran, E., Quarni, W., Nair, R., Stevens, S., Grinchuk, A., Hanna, A., Mohapatra, S., & Mohapatra, S. (2020). Lung cancer cells survive epidermal growth factor receptor tyrosine kinase inhibitor exposure through upregulation of cholesterol synthesis. FASEB BioAdvances, 2(2), 90–105. https://doi.org/10.1096/fba.2019-00081
  • Huang, F. (2012). Subclassifying disordered proteins by the CH-CDF plot method. Pacific Symposium on Biocomputing, 128–139.
  • Huang, F., Oldfield, C. J., Xue, B., Hsu, W.-L., Meng, J., Liu, X., Shen, L., Romero, P., Uversky, V. N., & Dunker, A. K. (2014). Improving protein order-disorder classification using charge-hydropathy plots. BMC Bioinformatics, 15(S17), S4. https://doi.org/10.1186/1471-2105-15-S17-S4
  • Iakoucheva, L. M., Brown, C. J., Lawson, J. D., Obradović, Z., & Dunker, A. K. (2002). Intrinsic disorder in cell-signaling and cancer-associated proteins. Journal of Molecular Biology, 323(3), 573–584. https://doi.org/10.1016/S0022-2836(02)00969-5
  • Jones, D. T. W., Kocialkowski, S., Liu, L., Pearson, D. M., Bäcklund, L. M., Ichimura, K., & Collins, V. P. (2008). Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Research, 68(21), 8673–8677. https://doi.org/10.1158/0008-5472.CAN-08-2097
  • Katayama, Y., Yamada, T., Tokuda, S., Okura, N., Nishioka, N., Morimoto, K., Tanimura, K., Morimoto, Y., Iwasaku, M., Horinaka, M., Sakai, T., Kita, K., Yano, S., & Takayama, K. (2022). Heterogeneity among tumors with acquired resistance to EGFR tyrosine kinase inhibitors harboring EGFR-T790M mutation in non-small cell lung cancer cells. Cancer Medicine, 11(4), 944–955. https://doi.org/10.1002/cam4.4504
  • Kesarwani, M., Kincaid, Z., Gomaa, A., Huber, E., Rohrabaugh, S., Siddiqui, Z., Bouso, M. F., Latif, T., Xu, M., Komurov, K., Mulloy, J. C., Cancelas, J. A., Grimes, H. L., & Azam, M. (2017). Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. Nature Medicine, 23(4), 472–482. https://doi.org/10.1038/nm.4310
  • Kim, D., Langmead, B., & Salzberg, S. L. (2015). HISAT: A fast spliced aligner with low memory requirements. Nature Methods, 12(4), 357–360. https://doi.org/10.1038/nmeth.3317
  • Kim, P. M., Sboner, A., Xia, Y., & Gerstein, M. (2008). The role of disorder in interaction networks: A structural analysis. Molecular Systems Biology, 4(179), 179.
  • Kim, S., Im, J. H., Kim, W. K., Choi, Y. J., Lee, J.-Y., Kim, S. K., Kim, S. J., Kwon, S. W., & Kang, K. W. (2021). Enhanced sensitivity of nonsmall cell lung cancer with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors to phenformin: The roles of a metabolic shift to oxidative phosphorylation and redox balance. Oxidative Medicine and Cellular Longevity, 2021, 5428364.
  • Kramer, A., et al. (2014). Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics, 30(4), 523–530.
  • Krause, D. S., & Van Etten, R. A. (2005). Tyrosine kinases as targets for cancer therapy. The New England Journal of Medicine, 353(2), 172–187. https://doi.org/10.1056/NEJMra044389
  • Kwapiszewski, R., Pawlak, S. D., & Adamkiewicz, K. (2016). Anti-EGFR agents: Current status, forecasts and future directions. Targeted Oncology, 11(6), 739–752. https://doi.org/10.1007/s11523-016-0456-3
  • Lee, C. S., Kim, K. L., Jang, J. H., Choi, Y. S., Suh, P.-G., & Ryu, S. H. (2009). The roles of phospholipase D in EGFR signaling. Biochimica et Biophysica Acta, 1791(9), 862–868. https://doi.org/10.1016/j.bbalip.2009.04.007
  • Liao, Y., Smyth, G. K., & Shi, W. (2014). featureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics (Oxford, England), 30(7), 923–930. https://doi.org/10.1093/bioinformatics/btt656
  • Lim, S. M., Syn, N. L., Cho, B. C., & Soo, R. A. (2018). Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies. Cancer Treatment Reviews, 65, 1–10. https://doi.org/10.1016/j.ctrv.2018.02.006
  • Lin, Y.-C., Lin, Y.-C., Shih, J.-Y., Huang, W.-J., Chao, S.-W., Chang, Y.-L., & Chen, C.-C. (2015). DUSP1 expression induced by HDAC1 inhibition mediates gefitinib sensitivity in non-small cell lung cancers. Clinical Cancer Research, 21(2), 428–438. https://doi.org/10.1158/1078-0432.CCR-14-1150
  • Love, M. I., Huber, W., & Anders, S. (2014). Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15(12), 550. https://doi.org/10.1186/s13059-014-0550-8
  • Martin, M. J., Eberlein, C., Taylor, M., Ashton, S., Robinson, D., & Cross, D. (2016). Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma. Oncotarget, 7(52), 86313–86325. https://doi.org/10.18632/oncotarget.13388
  • Mohan, A., Sullivan, W. J., Radivojac, P., Dunker, A. K., & Uversky, V. N. (2008). Intrinsic disorder in pathogenic and non-pathogenic microbes: Discovering and analyzing the unfoldomes of early-branching eukaryotes. Molecular bioSystems, 4(4), 328–340. https://doi.org/10.1039/b719168e
  • Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., & Dunker, A. K. (2005). Exploiting heterogeneous sequence properties improves prediction of protein disorder. Proteins: Structure, Function, and Bioinformatics, 61(S7), 176–182. https://doi.org/10.1002/prot.20735
  • Ohashi, K., Maruvka, Y. E., Michor, F., & Pao, W. (2013). Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. Journal of Clinical Oncology, 31(8), 1070–1080. https://doi.org/10.1200/JCO.2012.43.3912
  • Okimoto, R. A., Breitenbuecher, F., Olivas, V. R., Wu, W., Gini, B., Hofree, M., Asthana, S., Hrustanovic, G., Flanagan, J., Tulpule, A., Blakely, C. M., Haringsma, H. J., Simmons, A. D., Gowen, K., Suh, J., Miller, V. A., Ali, S., Schuler, M., & Bivona, T. G. (2017). Inactivation of Capicua drives cancer metastasis. Nature Genetics, 49(1), 87–96. https://doi.org/10.1038/ng.3728
  • Okon, I. S., Coughlan, K. A., Zhang, M., Wang, Q., & Zou, M.-H. (2015). Gefitinib-mediated reactive oxygen specie (ROS) instigates mitochondrial dysfunction and drug resistance in lung cancer cells. The Journal of Biological Chemistry, 290(14), 9101–9110. https://doi.org/10.1074/jbc.M114.631580
  • Oldfield, C. J., Cheng, Y., Cortese, M. S., Brown, C. J., Uversky, V. N., & Dunker, A. K. (2005). Comparing and combining predictors of mostly disordered proteins. Biochemistry, 44(6), 1989–2000. https://doi.org/10.1021/bi047993o
  • Oronsky, B., Ma, P., Reid, T. R., Cabrales, P., Lybeck, M., Oronsky, A., Oronsky, N., & Carter, C. A. (2018). Navigating the "no man’s land" of TKI-failed EGFR-mutated non-small cell lung cancer (NSCLC): A review. Neoplasia (New York, N.Y.), 20(1), 92–98. https://doi.org/10.1016/j.neo.2017.11.001
  • Papa, S., Choy, P. M., & Bubici, C. (2019). The ERK and JNK pathways in the regulation of metabolic reprogramming. Oncogene, 38(13), 2223–2240. https://doi.org/10.1038/s41388-018-0582-8
  • Parikh, P., & Puri, T. (2013). Personalized medicine: Lung Cancer leads the way. Indian Journal of Cancer, 50(2), 77–79. https://doi.org/10.4103/0019-509X.117005
  • Passaro, A., Jänne, P. A., Mok, T., & Peters, S. (2021). Overcoming therapy resistance in EGFR-mutant lung cancer. Nature Cancer, 2(4), 377–391. https://doi.org/10.1038/s43018-021-00195-8
  • Peacock, J. W., Takeuchi, A., Hayashi, N., Liu, L., Tam, K. J., Al Nakouzi, N., Khazamipour, N., Tombe, T., Dejima, T., Lee, K. C., Shiota, M., Thaper, D., Lee, W. C., Hui, D. H., Kuruma, H., Ivanova, L., Yenki, P., Jiao, I. Z., Khosravi, S., … Ong, C. J. (2018). SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1. EMBO Molecular Medicine, 10(2), 219–238. https://doi.org/10.15252/emmm.201707689
  • Peng, K., Radivojac, P., Vucetic, S., Dunker, A. K., & Obradovic, Z. (2006). Length-dependent prediction of protein intrinsic disorder. BMC Bioinformatics, 7(1), 208. https://doi.org/10.1186/1471-2105-7-208
  • Peng, K., Vucetic, S., Radivojac, P., Brown, C. J., Dunker, A. K., & Obradovic, Z. (2005). Optimizing long intrinsic disorder predictors with protein evolutionary information. Journal of Bioinformatics and Computational Biology, 3(1), 35–60. https://doi.org/10.1142/s0219720005000886
  • Pollack, V. A., Savage, D. M., Baker, D. A., Tsaparikos, K. E., Sloan, D. E., Moyer, J. D., Barbacci, E. G., Pustilnik, L. R., Smolarek, T. A., Davis, J. A., Vaidya, M. P., Arnold, L. D., Doty, J. L., Iwata, K. K., & Morin, M. J. (1999). Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: Dynamics of receptor inhibition in situ and antitumor effects in athymic mice. The Journal of Pharmacology and Experimental Therapeutics, 291(2), 739–748.
  • Romero, P., Obradovic, Z., Li, X., Garner, E. C., Brown, C. J., & Dunker, A. K. (2001). Sequence complexity of disordered protein. Proteins: Structure, Function, and Genetics, 42(1), 38–48. https://doi.org/10.1002/1097-0134(20010101)42:1<38::AID-PROT50>3.0.CO;2-3
  • Rosell, R., Cardona, A. F., Arrieta, O., Aguilar, A., Ito, M., Pedraz, C., Codony-Servat, J., & Santarpia, M. (2021). Coregulation of pathways in lung cancer patients with EGFR mutation: Therapeutic opportunities. British Journal of Cancer, 125(12), 1602–1611. https://doi.org/10.1038/s41416-021-01519-2
  • Scarborough, H. A., Helfrich, B. A., Casás-Selves, M., Schuller, A. G., Grosskurth, S. E., Kim, J., Tan, A.-C., Chan, D. C., Zhang, Z., Zaberezhnyy, V., Bunn, P. A., & DeGregori, J. (2017). AZ1366: An inhibitor of tankyrase and the canonical Wnt pathway that limits the persistence of non-small cell lung cancer cells following EGFR inhibition. Clinical Cancer Research, 23(6), 1531–1541. https://doi.org/10.1158/1078-0432.CCR-16-1179
  • Sen, M., Joyce, S., Panahandeh, M., Li, C., Thomas, S. M., Maxwell, J., Wang, L., Gooding, W. E., Johnson, D. E., & Grandis, J. R. (2012). Targeting Stat3 abrogates EGFR inhibitor resistance in cancer. Clinical Cancer Research, 18(18), 4986–4996. https://doi.org/10.1158/1078-0432.CCR-12-0792
  • Song, J.-Y., Kim, C.-S., Lee, J.-H., Jang, S. J., Lee, S-w., Hwang, J. J., Lim, C., Lee, G., Seo, J., Cho, S. Y., & Choi, J. (2013). Dual inhibition of MEK1/2 and EGFR synergistically induces caspase-3-dependent apoptosis in EGFR inhibitor-resistant lung cancer cells via BIM upregulation. Investigational New Drugs, 31(6), 1458–1465. https://doi.org/10.1007/s10637-013-0030-0
  • Song, K.-A., Hosono, Y., Turner, C., Jacob, S., Lochmann, T. L., Murakami, Y., Patel, N. U., Ham, J., Hu, B., Powell, K. M., Coon, C. M., Windle, B. E., Oya, Y., Koblinski, J. E., Harada, H., Leverson, J. D., Souers, A. J., Hata, A. N., Boikos, S., … Faber, A. C. (2018). Increased synthesis of MCL-1 protein underlies initial survival of EGFR-mutant lung cancer to EGFR inhibitors and provides a novel drug target. Clinical Cancer Research, 24(22), 5658–5672. https://doi.org/10.1158/1078-0432.CCR-18-0304
  • Sun, Y., Daemen, A., Hatzivassiliou, G., Arnott, D., Wilson, C., Zhuang, G., Gao, M., Liu, P., Boudreau, A., Johnson, L., & Settleman, J. (2014). Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4 as a mediator of epithelial-mesenchymal transition and drug resistance in tumor cells. Cancer & Metabolism, 2(1), 20. https://doi.org/10.1186/2049-3002-2-20
  • Tang, Z., Du, R., Jiang, S., Wu, C., Barkauskas, D. S., Richey, J., Molter, J., Lam, M., Flask, C., Gerson, S., Dowlati, A., Liu, L., Lee, Z., Halmos, B., Wang, Y., Kern, J. A., & Ma, P. C. (2008). Dual MET-EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer. British Journal of Cancer, 99(6), 911–922. https://doi.org/10.1038/sj.bjc.6604559
  • Tong, C. W. S., Wu, W. K. K., Loong, H. H. F., Cho, W. C. S., & To, K. K. W. (2017). Drug combination approach to overcome resistance to EGFR tyrosine kinase inhibitors in lung cancer. Cancer Letters, 405, 100–110. https://doi.org/10.1016/j.canlet.2017.07.023
  • Treue, D., Bockmayr, M., Stenzinger, A., Heim, D., Hester, S., & Klauschen, F. (2019). Proteogenomic systems analysis identifies targeted therapy resistance mechanisms in EGFR-mutated lung cancer. International Journal of Cancer, 144(3), 545–557. https://doi.org/10.1002/ijc.31845
  • Troiani, T., Napolitano, S., Della Corte, C. M., Martini, G., Martinelli, E., Morgillo, F., & Ciardiello, F. (2016). Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence. ESMO Open, 1(5), e000088. https://doi.org/10.1136/esmoopen-2016-000088
  • Uversky, V. N., Gillespie, J. R., & Fink, A. L. (2000). Why are "natively unfolded" proteins unstructured under physiologic conditions? Proteins: Structure, Function, and Genetics, 41(3), 415–427. https://doi.org/10.1002/1097-0134(20001115)41:3<415::AID-PROT130>3.0.CO;2-7
  • Van Bibber, N. W., et al. (2020). Intrinsic disorder in tetratricopeptide repeat proteins. International Journal of Molecular Sciences. (10), 21.
  • Ware, K. E., Hinz, T. K., Kleczko, E., Singleton, K. R., Marek, L. A., Helfrich, B. A., Cummings, C. T., Graham, D. K., Astling, D., Tan, A.-C., & Heasley, L. E. (2013). A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis, 2(3), e39. https://doi.org/10.1038/oncsis.2013.4
  • Wright, P. E., & Dyson, H. J. (1999). Intrinsically unstructured proteins: Re-assessing the protein structure-function paradigm. Journal of Molecular Biology, 293(2), 321–331. https://doi.org/10.1006/jmbi.1999.3110
  • Xia, W., Mullin, R. J., Keith, B. R., Liu, L.-H., Ma, H., Rusnak, D. W., Owens, G., Alligood, K. J., & Spector, N. L. (2002). Anti-tumor activity of GW572016: A dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene, 21(41), 6255–6263. https://doi.org/10.1038/sj.onc.1205794
  • Xue, B., Dunbrack, R. L., Williams, R. W., Dunker, A. K., & Uversky, V. N. (2010). PONDR-FIT: A meta-predictor of intrinsically disordered amino acids. Biochimica et Biophysica Acta, 1804(4), 996–1010. https://doi.org/10.1016/j.bbapap.2010.01.011
  • Xue, B., Oldfield, C. J., Dunker, A. K., & Uversky, V. N. (2009). CDF it all: Consensus prediction of intrinsically disordered proteins based on various cumulative distribution functions. FEBS Letters, 583(9), 1469–1474. https://doi.org/10.1016/j.febslet.2009.03.070
  • Yamaoka, T., Ohmori, T., Ohba, M., Arata, S., Kishino, Y., Murata, Y., Kusumoto, S., Ishida, H., Shirai, T., Hirose, T., Ohnishi, T., & Sasaki, Y. (2016). Acquired resistance mechanisms to combination Met-TKI/EGFR-TKI exposure in met-amplified EGFR-TKI-resistant lung adenocarcinoma harboring an activating EGFR mutation. Molecular Cancer Therapeutics, 15(12), 3040–3054. https://doi.org/10.1158/1535-7163.MCT-16-0313
  • Ye, M., Wang, S., Wan, T., Jiang, R., Qiu, Y., Pei, L., Pang, N., Huang, Y., Huang, Y., Zhang, Z., & Yang, L. (2017). Combined inhibitions of glycolysis and AKT/autophagy can overcome resistance to EGFR-targeted therapy of lung cancer. Journal of Cancer, 8(18), 3774–3784. https://doi.org/10.7150/jca.21035
  • Zhang, X.-Y., Zhang, Y.-K., Wang, Y.-J., Gupta, P., Zeng, L., Xu, M., Wang, X.-Q., Yang, D.-H., & Chen, Z.-S. (2016). Osimertinib (AZD9291), a mutant-selective EGFR inhibitor, reverses ABCB1-mediated drug resistance in cancer cells. Molecules, 21(9), 1236. https://doi.org/10.3390/molecules21091236
  • Zhang, Z., Kobayashi, S., Borczuk, A. C., Leidner, R. S., Laframboise, T., Levine, A. D., & Halmos, B. (2010). Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells. Carcinogenesis, 31(4), 577–586. https://doi.org/10.1093/carcin/bgq020
  • Zhao, C., Du, G., Skowronek, K., Frohman, M. A., & Bar-Sagi, D. (2007). Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nature Cell Biology, 9(6), 706–712. https://doi.org/10.1038/ncb1594
  • Zhong, W. Z., Zhou, Q., & Wu, Y. L. (2017). The resistance mechanisms and treatment strategies for EGFR-mutant advanced non-small-cell lung cancer. Oncotarget, 8(41), 71358–71370. https://doi.org/10.18632/oncotarget.20311

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.