Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.

Article  Google Scholar 

Guillermo Paez J, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–500.

Article  Google Scholar 

Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.

CAS  Article  Google Scholar 

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.

CAS  Article  Google Scholar 

Dogan S, Shen R, Ang DC, Johnson ML, D’Angelo SP, Paik PK, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18:6169–77.

CAS  Article  Google Scholar 

Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7:596–609.

CAS  Article  Google Scholar 

Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187–99.

CAS  Article  Google Scholar 

Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010;28:911–7.

CAS  Article  Google Scholar 

Kim C, Giaccone G. MEK inhibitors under development for treatment of non-small-cell lung cancer. Expert Opin Investig Drugs. 2018;27:17–30.

CAS  Article  Google Scholar 

Kaur M, Reed E, Sartor O, Dahut W, Figg WD. Suramin’s development: what did we learn? Invest New Drugs Springer. 2002;20:209–19.

CAS  Article  Google Scholar 

Rodriguez PC, Popa X, Martínez O, Mendoza S, Santiesteban E, Crespo T, et al. A phase III clinical trial of the epidermal growth factor vaccine CIMAvax-EGF as switch maintenance therapy in advanced non-small cell lung cancer patients. Clin Cancer Res. 2016;22:3782–90.

CAS  Article  Google Scholar 

Rosell R, Neninger E, Nicolson M, Huber RM, Thongprasert S, Parikh PM, et al. Pathway targeted immunotherapy: rationale and evidence of durable clinical responses with a novel, EGF-directed agent for advanced NSCLC. J Thorac Oncol. 2016;11:1954–61.

Article  Google Scholar 

Codony-Servat J, García-Roman S, Molina-Vila MÁ, Bertran-Alamillo J, Giménez-Capitán A, Viteri S, et al. Anti-epidermal growth factor vaccine antibodies enhance the efficacy of tyrosine kinase inhibitors and delay the emergence of resistance in EGFR mutant lung cancer cells. J Thorac Oncol. 2018;13:1324–37.

Article  Google Scholar 

Rodríguez-Abreu D, Cobo M, García-Román S, Viteri-Ramírez S, Jordana-Ariza N, García-Peláez B, et al. The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic NSCLC. Lung Cancer. 2022;164:8–13.

Article  Google Scholar 

Guardiola S, Varese M, Sánchez-Navarro M, Giralt E. A third shot at EGFR: new opportunities in cancer therapy. Trends Pharmacol Sci. 2019;40:941–55.

CAS  Article  Google Scholar 

Yang EY, Shah K. Nanobodies: next generation of cancer diagnostics and therapeutics. Front Oncol. 2020;10:1182.

CAS  Article  Google Scholar 

Guardiola S, Varese M, Sánchez-Navarro M, Vincke C, Teixidó M, García J, et al. Blocking EGFR activation with anti-EGF nanobodies via two distinct molecular recognition mechanisms. Angew Chem Int Ed Engl. 2018;57:13843–7.

CAS  Article  Google Scholar 

Codony-Servat J, García-Roman S, Molina-Vila MÁ, Bertran-Alamillo J, Viteri S, d’Hondt E, et al. Anti-epidermal growth factor vaccine antibodies increase the antitumor activity of kinase inhibitors in ALK and RET rearranged lung cancer cells. Transl Oncol. 2021;14:100887.

Article  Google Scholar 

Tricker EM, Xu C, Uddin S, Capelletti M, Ercan D, Ogino A, et al. Combined EGFR/MEK inhibition prevents the emergence of resistance in EGFR-mutant lung cancer. Cancer Discov Cancer Discov. 2015;5:960–71.

CAS  Article  Google Scholar 

Guardiola S, Varese M, Taulés M, Díaz-Lobo M, García J, Giralt E. Probing the kinetic and thermodynamic fingerprints of anti-EGF nanobodies by surface plasmon resonance. Pharmaceuticals. 2020;13:134.

CAS  Article  Google Scholar 

Codony-Servat J, Viteri S, Codony-Servat C, Ito M, Bracht JWP, Berenguer J, et al. Hsp90 inhibitors enhance the antitumoral effect of osimertinib in parental and osimertinib-resistant non-small cell lung cancer cell lines. Transl Lung Cancer Res. 2019;8:340.

CAS  Article  Google Scholar 

Qu F, Zhou Y, Yu W. A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance. Anticancer Drugs. 2022;33:e76.

CAS  Article  Google Scholar 

Nanamiya R, Saito-Koyama R, Miki Y, Inoue C, Asavasupreechar T, Abe J, et al. EphB4 as a novel target for the EGFR-independent suppressive effects of osimertinib on cell cycle progression in non-small cell lung cancer. Int J Mol Sci. 2021;22:8522.

CAS  Article  Google Scholar 

Guardiola S, Díaz-Lobo M, Seco J, García J, Nevola L, Giralt E. Peptides targeting EGF block the EGF-EGFR interaction. ChemBioChem. 2016;17:702–11.

CAS  Article  Google Scholar 

Guardiola S, Seco J, Varese M, Díaz-Lobo M, García J, Teixidó M, et al. Toward a novel drug to target the EGF-EGFR interaction: design of metabolically stable bicyclic peptides. ChemBioChem. 2018;19:76–84.

CAS  Article  Google Scholar 

Chen T, Liu X, Hong H, Wei H. Novel single-domain antibodies against the EGFR domain III epitope exhibit the anti-tumor effect. J Transl Med BioMed Central. 2020;18:1–16.

Google Scholar 

Altintas I, Heukers R, van der Meel R, Lacombe M, Amidi M, van Bergen En Henegouwen PM, et al. Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells. J Control Release. 2013;165:110–8.

CAS  Article  Google Scholar 

Wegner KD, Lindén S, Jin Z, Jennings TL, el Khoulati R, van Bergen en Henegouwen PM, et al. Nanobodies and nanocrystals: highly sensitive quantum dot-based homogeneous FRET immunoassay for serum-based EGFR detection. Small. 2014;10:734–40.

CAS  Article  Google Scholar 

Albert S, Arndt C, Koristka S, Berndt N, Bergmann R, Feldmann A, et al. From mono- to bivalent: improving theranostic properties of target modules for redirection of UniCAR T cells against EGFR-expressing tumor cells in vitro and in vivo. Oncotarget. 2018;9:25597.

Article  Google Scholar 

van Pbaa D, Boonstra MC, Slooter MD, Heukers R, Stammes MA, Snoeks TJA, et al. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J Control Release. 2016;229:93–105.

Article  Google Scholar 

Zhang Q, Wu L, Liu S, Chen Q, Zeng L, Chen X, et al. Targeted nanobody complex enhanced photodynamic therapy for lung cancer by overcoming tumor microenvironment. Cancer Cell Int. 2020;20:1–16.

Article  Google Scholar 

Liu Z-H, Dai X-M, Du B. Hes1: a key role in stemness, metastasis and multidrug resistance. Cancer Biol Ther. 2015;16:353–9.

CAS  Article  Google Scholar 

Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, et al. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res. 2013;19:279–90.

CAS  Article  Google Scholar 

Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012;44:852–60.

CAS  Article  Google Scholar 

Zhang X, Tian T, Sun W, Liu C, Fang X. Bmi-1 overexpression as an efficient prognostic marker in patients with nonsmall cell lung cancer. Medicine. 2017;96:e7346.

CAS  Article  Google Scholar 

Wang R, Fan H, Sun M, Lv Z, Yi W. Roles of BMI1 in the initiation, progression, and treatment of hepatocellular carcinoma. Technol Cancer Res Treat. 2022;21:15330338211070688.

PubMed  PubMed Central  Google Scholar 

Fang Z, Lin M, Li C, Liu H, Gong C. A comprehensive review of the roles of E2F1 in colon cancer. Am J Cancer Res. 2020;10:757.

CAS  PubMed  PubMed Central  Google Scholar 

Jänicke RU, Sohn D, Essmann F, Schulze-Osthoff K. The multiple battles fought by anti-apoptotic p21. Cell Cycle. 2007;6:407–13.

Article  Google Scholar 

Karimian A, Ahmadi Y, Yousefi B. Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair DNA Repair (Amst). 2016;42:63–71.

CAS  Article  Google Scholar