Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.
Paez JG, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–500. https://doi.org/10.1126/science.1099314.
Gallardo E, Navarro A, Viñolas N, Marrades RM, Diaz T, Gel B, et al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis. 2009;30(11):1903–9. https://doi.org/10.1093/carcin/bgp219.
Normanno N, de Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366(1):2–16. https://doi.org/10.1016/j.gene.2005.10.018.
Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004;59(2):S21–6. https://doi.org/10.1016/j.ijrobp.2003.11.041.
Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131(6):1190–203. https://doi.org/10.1016/j.cell.2007.11.025.
Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169–81. https://doi.org/10.1038/nrc2088.
Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, et al. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non–small-cell lung cancer and other solid tumors: results of a phase I trial. J Clin Oncol. 2002;20(18):3815–25. https://doi.org/10.1200/JCO.2002.03.038.
Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 2004;305(5687):1163–7. https://doi.org/10.1126/science.1101637.
Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non–small-cell lung cancer to gefitinib. N Engl J Med. 2005;352(8):786–92. https://doi.org/10.1056/NEJMoa044238.
Ghosh A, Yan H. Hydrogen bond analysis of the EGFR-ErbB3 heterodimer related to non-small cell lung cancer and drug resistance. J Theor Biol. 2019;464:63–71. https://doi.org/10.1016/j.jtbi.2018.12.035.
Yun C-H, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci. 2008;105(6):2070–5. https://doi.org/10.1073/pnas.0709662105.
Zou B, Lee VH, Yan H. Prediction of sensitivity to gefitinib/erlotinib for EGFR mutations in NSCLC based on structural interaction fingerprints and multilinear principal component analysis. BMC Bioinformatics. 2018;19(1):1–13.
Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci. 2007;104(52):20932–7. https://doi.org/10.1073/pnas.0710370104.
Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. science. 2007;316(5827):1039–43. https://doi.org/10.1126/science.1141478.
D. D. Wang, L. Ma, M. P. Wong, V. H. Lee, and H. Yan, "Contribution of EGFR and ErbB-3 heterodimerization to the EGFR mutation-induced gefitinib-and erlotinib-resistance in non-small-cell lung carcinoma treatments," PloS one, vol. 10, no. 5, p. e0128360, 2015.
Ahmad T, Farnie G, Bundred NJ, Anderson NG. The mitogenic action of insulin-like growth factor I in normal human mammary epithelial cells requires the epidermal growth factor receptor tyrosine kinase. J Biol Chem. 2004;279(3):1713–9. https://doi.org/10.1074/jbc.M306156200.
Jones HE, Goddard L, Gee JMW, Hiscox S, Rubini M, Barrow D, et al. Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer. 2004;11(4):793–814. https://doi.org/10.1677/erc.1.00799.
F. Cappuzzo et al., "Increased MET gene copy number negatively affects survival of surgically resected non–small-cell lung cancer patients," Journal of Clinical Oncology, vol. 27, no. 10, p. 1667, 2009.
Jo M, Stolz DB, Esplen JE, Dorko K, Michalopoulos GK, Strom SC. Cross-talk between epidermal growth factor receptor and c-met signal pathways in transformed cells. J Biol Chem. 2000;275(12):8806–11. https://doi.org/10.1074/jbc.275.12.8806.
E. Ortiz-Zapater et al., "MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition," PLoS One, vol. 12, no. 1, p. e0170798, 2017.
Tanizaki J, Okamoto I, Sakai K, Nakagawa K. Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification. Br J Cancer. 2011;105(6):807–13. https://doi.org/10.1038/bjc.2011.322.
Wheeler DL, Huang S, Kruser TJ, Nechrebecki MM, Armstrong EA, Benavente S, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene. 2008;27(28):3944–56. https://doi.org/10.1038/onc.2008.19.
M.-L. I. Harwardt et al., "Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation," International Journal of Molecular Sciences, vol. 21, no. 8, p. 2803, 2020.
J. Knowles and Z. Gechtman, "Probing EGFR, HER2, and c-Met Protein-Protein Interactions Using an Antibody Array," in Molecular Cancer Therapeutics, 2013, vol. 12, no. 11: AMER ASSOC CANCER RESEARCH 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA … .
R. Lee et al., "T6 MET targeted therapy in lung adenocarcinoma: does ‘resistant’EGFR make a MET-responsive dimer?," ed: BMJ publishing group ltd, 2015.
Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65(23):11118–28. https://doi.org/10.1158/0008-5472.CAN-04-3841.
Iyer G, Price J, Bourgeois S, Armstrong E, Huang S, Harari PM. Insulin growth factor 1 like receptor (IGF-1R). BMC Cancer. 2016;16(1):1–11.
Oliveira S, Schiffelers R, Storm G, Henegouwen P, Roovers R. Crosstalk between epidermal growth factor receptor-and insulin-like growth factor-1 receptor signaling: implications for cancer therapy. Curr Cancer Drug Targets. 2009;9(6):748–60.
Morgillo F, Woo JK, Kim ES, Hong WK, Lee H-Y. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Res. 2006;66(20):10100–11. https://doi.org/10.1158/0008-5472.CAN-06-1684.
M. A. Becker and D. Yee, "Crosstalk Between Insulin-like Growth Factor (IGF) and Epidermal Growth Factor (EGF) Receptors," in EGFR Signaling Networks in Cancer Therapy: Springer, 2008, pp. 147–160.
Tang Z, du R, Jiang S, Wu C, Barkauskas DS, Richey J, et al. Dual MET–EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer. Br J Cancer. 2008;99(6):911–22. https://doi.org/10.1038/sj.bjc.6604559.
Xu H, Stabile LP, Gubish CT, Gooding WE, Grandis JR, Siegfried JM. Dual blockade of EGFR and c-met abrogates redundant signaling and proliferation in head and neck carcinoma cells. Clin Cancer Res. 2011;17(13):4425–38. https://doi.org/10.1158/1078-0432.CCR-10-3339.
Berasain C, Ujue Latasa M, Urtasun R, Goñi S, Elizalde M, Garcia-Irigoyen O, et al. Epidermal growth factor receptor (EGFR) crosstalks in liver cancer. Cancers. 2011;3(2):2444–61. https://doi.org/10.3390/cancers3022444.
A. Dixit and G. M. Verkhivker, "Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases," PLoS computational biology, vol. 7, no. 10, p. e1002179, 2011.
Ma L, Wang DD, Huang Y, Wong MP, Lee VH, Yan H. Decoding the EGFR mutation-induced drug resistance in lung cancer treatment by local surface geometric properties. Comput Biol Med. 2015;63:293–300. https://doi.org/10.1016/j.compbiomed.2014.06.016.
L. Ma, B. Zou, and H. Yan, "Identifying EGFR mutation-induced drug resistance based on alpha shape model analysis of the dynamics," Proteome science, vol. 14, no. 1, p. 12, 2016.
Shan Y, Arkhipov A, Kim ET, Pan AC, Shaw DE. Transitions to catalytically inactive conformations in EGFR kinase. Proc Natl Acad Sci. 2013;110(18):7270–5. https://doi.org/10.1073/pnas.1220843110.
Shan Y, Eastwood MP, Zhang X, Kim ET, Arkhipov A, Dror RO, et al. Oncogenic mutations counteract intrinsic disorder in the EGFR kinase and promote receptor dimerization. Cell. 2012;149(4):860–70. https://doi.org/10.1016/j.cell.2012.02.063.
M. Z. Tamirat, K. J. Kurppa, K. Elenius, and M. S. Johnson, "Deciphering the structural effects of activating EGFR somatic mutations with molecular dynamics simulation," JoVE (Journal of Visualized Experiments), no. 159, p. e61125, 2020.
M. Z. Tamirat, M. Koivu, K. Elenius, and M. S. Johnson, "Structural characterization of EGFR exon 19 deletion mutation using molecular dynamics simulation," PloS one, vol. 14, no. 9, p. e0222814, 2019.
Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, et al. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell. 2006;9(6):485–95. https://doi.org/10.1016/j.ccr.2006.04.022.
L. V. Sequist et al., "Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors," Science translational medicine, vol. 3, no. 75, pp. 75ra26-75ra26, 2011.
Ni Z, Wang X, Zhang T, Jin RZ. Molecular dynamics simulations reveal the allosteric effect of F1174C resistance mutation to ceritinib in ALK-associated lung cancer. Comput Biol Chem. 2016;65:54–60. https://doi.org/10.1016/j.compbiolchem.2016.10.005.
H. Edelsbrunner, Weighted alpha shapes. University of Illinois at Urbana-Champaign, 1992.
Edelsbrunner H, Mücke EP. Three-dimensional alpha shapes. ACM Transactions on Graphics (TOG). 1994;13(1):43–72. https://doi.org/10.1145/174462.156635.
Ma L, Wang DD, Huang Y, Yan H, Wong MP, Lee VH. EGFR mutant structural database: computationally predicted 3D structures and the corresponding binding free energies with gefitinib and erlotinib. BMC Bioinformatics. 2015;16(1):1–10.
Song Y, DiMaio F, Wang RYR, Kim D, Miles C, Brunette T, et al. "High-resolution comparative modeling with RosettaCM". Structure. 2013;21(10):1735–42.
Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell. 2006;125(6):1137–49. https://doi.org/10.1016/j.cell.2006.05.013.
Simons KT, Kooperberg C, Huang E, Baker D. Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and Bayesian scoring functions. J Mol Biol. 1997;268(1):209–25. https://doi.org/10.1006/jmbi.1997.0959.
Robetta. "Full-chain Protein Structure Prediction Server." (accessed 12-June, 2019).
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12. https://doi.org/10.1002/jcc.20084.
Aertgeerts K, Skene R, Yano J, Sang BC, Zou H, Snell G, et al. Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. J Biol Chem. 2011;286(21):18756–65. https://doi.org/10.1074/jbc.M110.206193.
Wu K, Ai J, Liu Q, Chen TT, Zhao A, Peng X, et al. Multisubstituted quinoxalines and pyrido [2, 3-d] pyrimidines: synthesis and SAR study as tyrosine kinase c-met inhibitors. Bioorg Med Chem Lett. 2012;22(20):6368–72. https://doi.org/10.1016/j.bmcl.2012.08.075.
Degorce SBL, et al. Discovery of a potent, selective, orally bioavailable, and efficacious novel 2-(pyrazol-4-ylamino)-pyrimidine inhibitor of the insulin-like growth factor-1 receptor (IGF-1R). J Med Chem. 2016;59(10):4859–66. https://doi.org/10.1021/acs.jmedchem.6b00203.
D. Frenkel and B. Smit, Understanding molecular simulation: from algorithms to applications. Elsevier, 2001.
R. M. B. D.A. Case, D.S. Cerutti, T.E. Cheatham, III, T.A. Darden, R.E. Duke, T.J. Giese, H. Gohlke, A.W. Goetz, N. Homeyer, S. Izadi, P. Janowski, J. Kaus, A. Kovalenko, T.S. Lee, S. Legrand, P. Li C. and T. L. Lin, R. Luo, B. Madej, D. Mermelstein, K.M. Merz, G. Monard, H. Nguyen, H.T. Nguyen, I. Omelyan, A. Onufriev, D.R. Roe, A. Roitberg, C. Sagui, C.L. Simmerling, W.M. Botello-Smith, J. Swails, R.C. Walker, J. Wang, R.M. Wolf, X. Wu, L. Xiao and P.A. Kollman, "AMBER 2016," 2016.
F. Bernardini and C. L. Bajaj, "Sampling and reconstructing manifolds using alpha-shapes," 1997.
Guibas L, Stolfi J. Primitives for the manipulation of general subdivisions and the computation of Voronoi. ACM transactions on graphics (TOG). 1985;4(2):74–123. https://doi.org/10.1145/282918.282923.
CGAL. "Computational Geometry Algorithms Library. 1996. [online] Available: https://www.cgal.org/.
Zhou W, Yan H, Hao Q. Analysis of surface structures of hydrogen bonding in protein–ligand interactions using the alpha shape model. Chem Phys Lett. 2012;545:125–31. https://doi.org/10.1016/j.cplett.2012.07.016.
Roe DR, Cheatham TE III. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–95. https://doi.org/10.1021/ct400341p.
Srivastava HK, Sastry GN. Molecular dynamics investigation on a series of HIV protease inhibitors: assessing the performance of MM-PBSA and MM-GBSA approaches. J Chem Inf Model. 2012;52(11):3088–98. https://doi.org/10.1021/ci300385h.