Review

Current and future targeted therapies for non-small-cell lung cancers with aberrant EGF receptors

Shanthi Kanthala

Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA

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Sandeep Pallerla

Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA

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Seetharama Jois

*Author for correspondence:

E-mail Address: jois@ulm.edu

Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA

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Published Online:11 Mar 2015https://doi.org/10.2217/fon.14.312

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Abstract

ABSTRACT

Expression of the EGF receptors (EGFRs) is abnormally high in many types of cancer, including 25% of lung cancers. Successful treatments target mutations in the EGFR tyrosine kinase domain with EGFR tyrosine kinase inhibitors (TKIs). However, almost all patients develop resistance to this treatment, and acquired resistance to first-generation TKI has prompted the clinical development of a second generation of EGFR TKI. Because of the development of resistance to treatment of TKIs, there is a need to collect genomic information about EGFR levels in non-small-cell lung cancer patients. Herein, we focus on current molecular targets that have therapies available as well as other targets for which therapies will be available in the near future.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J. Clin. 63(1), 11–30 (2013).Crossref, Medline, Google Scholar
2 Ferketich AK, Niland JC, Mamet R et al. Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort. Cancer 119(4), 847–853 (2013).•• Provides information about population with lung cancer that never smoked.Crossref, Medline, Google Scholar
3 Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 23(Suppl. 7), vii56–vii64 (2012).Crossref, Medline, Google Scholar
4 Davidson MR, Gazdar AF, Clarke BE. The pivotal role of pathology in the management of lung cancer. J. Thorac. Dis. 5(Suppl. 5), S463–S478 (2013).Medline, Google Scholar
5 Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The evolving role of histology in the management of advanced non-small-cell lung cancer. J. Clin. Oncol. 28(36), 5311–5320 (2010).Crossref, Medline, Google Scholar
6 Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat. Rev. Cancer 14(8), 535–546 (2014).Crossref, Medline, CAS, Google Scholar
7 Calikusu Z, Yildirim Y, Akcali Z et al. The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients. J. Exp. Clin. Cancer Res. 28, 97 (2009).Crossref, Medline, Google Scholar
8 Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clin. Chest Med. 32(4), 605–644 (2011).Crossref, Medline, Google Scholar
9 Schabath MB, Thompson ZJ, Gray JE. Temporal trends in demographics and overall survival of non-small-cell lung cancer patients at Moffitt Cancer Center from 1986 to 2008. Cancer Control 21(1), 51–56 (2014).Crossref, Medline, Google Scholar
10 McErlean A, Ginsberg MS. Epidemiology of lung cancer. Semin. Roentgenol. 46(3), 173–177 (2011).Crossref, Medline, Google Scholar
11 Savas P, Hughes B, Solomon B. Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer. J. Thorac. Dis. 5(Suppl. 5), S579–592 (2013).Medline, Google Scholar
12 Nguyen KS, Neal JW, Wakelee H. Review of the current targeted therapies for non-small-cell lung cancer. World J. Clin. Oncol. 5(4), 576–587 (2014).Crossref, Medline, Google Scholar
13 Stinchcombe TE. Novel agents in development for advanced non-small cell lung cancer. Ther. Adv. Med. Oncol. 6(5), 240–253 (2014).Crossref, Medline, CAS, Google Scholar
14 Salgia R. Fibroblast growth factor signaling and inhibition in non-small cell lung cancer and their role in squamous cell tumors. Cancer Med. 3(3), 681–692 (2014).Crossref, Medline, CAS, Google Scholar
15 Reungwetwattana T, Dy GK. Targeted therapies in development for non-small cell lung cancer. J. Carcinog. 12, 22 (2013).Crossref, Medline, Google Scholar
16 Hirsch FR, Varella-Garcia M, Cappuzzo F. Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer. Oncogene 28(Suppl. 1), S32–S37 (2009).Crossref, Medline, CAS, Google Scholar
17 Makinoshima H, Takita M, Matsumoto S et al. Epidermal growth factor receptor (EGFR) signaling regulates global metabolic pathways in EGFR-mutated lung adenocarcinoma. J. Biol. Chem. 289(30), 20813–20823 (2014).Crossref, Medline, CAS, Google Scholar
18 Castro A.C.G, Felip E. HER2 driven non-small lung cancer (NSCLC): potential therapeutic approaches. Transl. Lung Cancer Res. 2(2), 122–127 (2013).Medline, Google Scholar
19 Krug LM, Miller VA, Patel J et al. Randomized Phase II study of weekly docetaxel plus trastuzumab versus weekly paclitaxel plus trastuzumab in patients with previously untreated advanced nonsmall cell lung carcinoma. Cancer 104(10), 2149–2155 (2005).Crossref, Medline, CAS, Google Scholar
20 Cappuzzo F, Bemis L, Varella-Garcia M. HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N. Engl. J. Med. 354(24), 2619–2621 (2006).Crossref, Medline, CAS, Google Scholar
21 De Greve J, Teugels E, Geers C et al. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer 76(1), 123–127 (2012).Crossref, Medline, CAS, Google Scholar
22 Zeng S, Yang Y, Tan Y et al. ERBB2-induced inflammation in lung carcinogenesis. Mol. Biol. Rep. 39(8), 7911–7917 (2012).Crossref, Medline, CAS, Google Scholar
23 Mazieres J, Peters S, Lepage B et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J. Clin. Oncol. 31(16), 1997–2003 (2013).• Details of HER2 mutation in treatment of lung cancer.Crossref, Medline, CAS, Google Scholar
24 Arcila ME, Chaft JE, Nafa K et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. Cancer Res. 18(18), 4910–4918 (2012).Crossref, Medline, CAS, Google Scholar
25 Yan M, Parker BA, Schwab R, Kurzrock R. HER2 aberrations in cancer: implications for therapy. Cancer Treat. Rev. 40(6), 770–780 (2014).• Discusses importance of HER2 and treatment option based on mutation.Crossref, Medline, CAS, Google Scholar
26 Menju T, Hashimoto S, Hashimoto A et al. Engagement of overexpressed Her2 with GEP100 induces autonomous invasive activities and provides a biomarker for metastases of lung adenocarcinoma. PLoS ONE 6(9), e25301 (2011).Crossref, Medline, CAS, Google Scholar
27 Brabender J, Danenberg KD, Metzger R et al. Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival. Clin. Cancer Res. 7(7), 1850–1855 (2001).Medline, CAS, Google Scholar
28 Noto A, De Vitis C, Roscilli G et al. Combination therapy with anti-ErbB3 monoclonal antibodies and EGFR TKIs potently inhibits non-small cell lung cancer. Oncotarget 4(8), 1253–1265 (2013).Crossref, Medline, Google Scholar
29 Ma J, Lyu H, Huang J, Liu B. Targeting of erbB3 receptor to overcome resistance in cancer treatment. Mol. Cancer 13, 105 (2014).•• Novel method that uses HER3 for EGFR-mutated lung cancer.Crossref, Medline, Google Scholar
30 Amin DN, Campbell MR, Moasser MM. The role of HER3, the unpretentious member of the HER family, in cancer biology and cancer therapeutics. Semin. Cell Dev. Biol. 21(9), 944–950 (2010).Crossref, Medline, CAS, Google Scholar
31 Roengvoraphoj M, Tsongalis GJ, Dragnev KH, Rigas JR. Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients. Cancer Treat. Rev. 39(8), 839–850 (2013).Crossref, Medline, CAS, Google Scholar
32 Villaflor VM, Salgia R. Targeted agents in non-small cell lung cancer therapy: What is there on the horizon? J. Carcinog. 12, 7 (2013).Crossref, Medline, CAS, Google Scholar
33 Wu JY, Wu SG, Yang CH et al. Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin. Cancer Res. 14(15), 4877–4882 (2008).Crossref, Medline, CAS, Google Scholar
34 Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 13(1), e23–e31 (2012).Crossref, Medline, CAS, Google Scholar
35 Lee CC, Shiao HY, Wang WC, Hsieh HP. Small-molecule EGFR tyrosine kinase inhibitors for the treatment of cancer. Expert Opin. Investig. Drugs 23(10), 1333–1348 (2014).Crossref, Medline, CAS, Google Scholar
36 Yang SH. Molecular basis of drug resistance: epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors. Tuberc. Respir. Dis. (Seoul) 75(5), 188–198 (2013).Crossref, Medline, Google Scholar
37 Weber B, Meldgaard P, Hager H et al. Detection of EGFR mutations in plasma and biopsies from non-small cell lung cancer patients by allele-specific PCR assays. BMC Cancer 14, 294 (2014).Crossref, Medline, Google Scholar
38 Brevet M, Arcila M, Ladanyi M. Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR. J. Mol. Diagn. 12(2), 169–176 (2010).Crossref, Medline, CAS, Google Scholar
39 Nanavaty P, Alvarez MS, Alberts WM. Lung cancer screening: advantages, controversies, and applications. Cancer Control 21(1), 9–14 (2014).Crossref, Medline, Google Scholar
40 Li T, Kung HJ, Mack PC, Gandara DR. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J. Clin. Oncol. 31(8), 1039–1049 (2013).Crossref, Medline, CAS, Google Scholar
41 Tanvetyanon T, Creelan BC, Chiappori AA. Current clinical application of genomic and proteomic profiling in non-small-cell lung cancer. Cancer Control 21(1), 32–39 (2014).Crossref, Medline, Google Scholar
42 Huber RM, Reck M, Thomas M. Current status of and future strategies for multimodality treatment of unresectable stage III nonsmall cell lung cancer. Eur. Respir. J. 42(4), 1119–1133 (2013).Crossref, Medline, Google Scholar
43 Aberle DR, Adams AM, Berg CD et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med. 365(5), 395–409 (2011).Crossref, Medline, Google Scholar
44 Horeweg N, Nackaerts K, Oudkerk M, De Koning HJ. Low-dose computed tomography screening for lung cancer: results of the first screening round. J. Comp. Eff. Res. 2(5), 433–436 (2013).Link, Google Scholar
45 Church TR, Black WC, Aberle DR et al. Results of initial low-dose computed tomographic screening for lung cancer. N. Engl. J. Med. 368(21), 1980–1991 (2013).Crossref, Medline, Google Scholar
46 Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med. 353(2), 123–132 (2005).Crossref, Medline, CAS, Google Scholar
47 Grandis JR, Sok JC. Signaling through the epidermal growth factor receptor during the development of malignancy. Pharmacol. Ther. 102(1), 37–46 (2004).Crossref, Medline, CAS, Google Scholar
48 Tsao AS, Papadimitrakopoulou V. The importance of molecular profiling in predicting response to epidermal growth factor receptor family inhibitors in non-small-cell lung cancer: focus on clinical trial results. Clin. Lung Cancer 14(4), 311–321 (2013).Crossref, Medline, CAS, Google Scholar
49 Asami K, Atagi S. Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer. World J. Clin. Oncol. 5(4), 646–659 (2014).Crossref, Medline, Google Scholar
50 Scagliotti GV, Parikh P, Von Pawel J et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J. Clin. Oncol. 26(21), 3543–3551 (2008).Crossref, Medline, CAS, Google Scholar
51 Scagliotti G, Brodowicz T, Shepherd FA et al. Treatment-by-histology interaction analyses in three Phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer. J. Thorac. Oncol. 6(1), 64–70 (2011).Crossref, Medline, Google Scholar
52 Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355(24), 2542–2550 (2006).Crossref, Medline, CAS, Google Scholar
53 Velcheti V, Morgensztern D, Govindan R. Management of patients with advanced non-small cell lung cancer: role of gefitinib. Biologics 4, 83–90 (2010).Medline, CAS, Google Scholar
54 Khozin S, Blumenthal GM, Jiang X et al. U.S. Food and Drug Administration approval summary. Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. Oncologist 19(7), 774–779 (2014).Crossref, Medline, CAS, Google Scholar
55 Reckamp KL, Giaccone G, Camidge DR et al. A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib. Cancer 120(8), 1145–1154 (2014).Crossref, Medline, CAS, Google Scholar
56 Gandhi L, Bahleda R, Tolaney SM et al. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J. Clin. Oncol. 32(2), 68–75 (2014).Crossref, Medline, CAS, Google Scholar
57 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. 28(18), 3076–3083 (2010).Crossref, Medline, CAS, Google Scholar
58 Cha MY, Lee KO, Kim M et al. Antitumor activity of HM781–36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models. Int. J. Cancer 130(10), 2445–2454 (2012).Crossref, Medline, CAS, Google Scholar
59 AZD9291 Could Be an Option for NSCLC. Cancer Discov. 4(8), OF10 (2014).Crossref, Google Scholar
60 Peters S, Zimmermann S, Adjei AA. Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: Comparative pharmacokinetics and drug-drug interactions. Cancer Treat. Rev. 40(8), 917–926 (2014).Crossref, Medline, CAS, Google Scholar
61 Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised Phase III trial. Lancet 373(9674), 1525–1531 (2009).Crossref, Medline, CAS, Google Scholar
62 Dienstmann R, Felip E. Necitumumab in the treatment of advanced non-small cell lung cancer: translation from preclinical to clinical development. Expert Opin. Biol. Ther. 11(9), 1223–1231 (2011).Crossref, Medline, CAS, Google Scholar
63 Crawford J, Swanson P, Schwarzenberger P et al. A phase 2 randomized trial of paclitaxel and carboplatin with or without panitumumab for first-line treatment of advanced non-small-cell lung cancer. J. Thorac. Oncol. 8(12), 1510–1518 (2013).Crossref, Medline, CAS, Google Scholar
64 Babu KG, Prabhash K, Vaid AK et al. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer. a multicenter, randomized, open-label Phase I study. Onco Targets Ther. 7, 1051–1060 (2014).Crossref, Medline, Google Scholar
65 Schiller JH, Von Pawel J, Schutt P et al. Pemetrexed with or without matuzumab as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer. J. Thorac. Oncol. 5(12), 1977–1985 (2010).Crossref, Medline, Google Scholar
66 Saloura V, Cohen EE, Licitra L et al. An open-label single-arm, Phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother. Pharmacol. 73(6), 1227–1239 (2014).Crossref, Medline, CAS, Google Scholar
67 Barthelemy P, Leblanc J, Goldbarg V, Wendling F, Kurtz JE. Pertuzumab: development beyond breast cancer. Anticancer Res. 34(4), 1483–1491 (2014).Medline, CAS, Google Scholar
68 Hughes B, Mileshkin L, Townley P et al. Pertuzumab and erlotinib in patients with relapsed non-small cell lung cancer. a Phase II study using 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Oncologist 19(2), 175–176 (2014).Crossref, Medline, Google Scholar
69 Janjigian YY, Azzoli CG, Krug LM et al. Phase I/II trial of cetuximab and erlotinib in patients with lung adenocarcinoma and acquired resistance to erlotinib. Clin. Cancer Res. 17(8), 2521–2527 (2011).Crossref, Medline, CAS, Google Scholar
70 Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 69(24), 9330–9336 (2009).Crossref, Medline, CAS, Google Scholar
71 Chen X, Zhu Q, Liu Y et al. Icotinib is an active treatment of non-small-cell lung cancer. a retrospective study. PLoS ONE 9(5), e95897 (2014).Crossref, Medline, Google Scholar
72 Pirker R, Pereira JR, Von Pawel J et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer. analysis of data from the Phase 3 FLEX study. Lancet Oncol. 13(1), 33–42 (2012).Crossref, Medline, CAS, Google Scholar
73 Hirsch FR, Herbst RS, Olsen C et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J. Clin. Oncol. 26(20), 3351–3357 (2008).Crossref, Medline, CAS, Google Scholar
74 Shien K, Yamamoto H, Soh J, Miyoshi S, Toyooka S. Drug resistance to EGFR tyrosine kinase inhibitors for non-small cell lung cancer. Acta Medica Okayama 68(4), 191–200 (2014).Medline, CAS, Google Scholar
75 Regales L, Gong Y, Shen R et al. Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J. Clin. Invest. 119(10), 3000–3010 (2009).Medline, CAS, Google Scholar
76 Zhang H, Yun S, Batuwangala TD et al. A dual-targeting antibody against EGFR-VEGF for lung and head and neck cancer treatment. Int. J. Cancer 131(4), 956–969 (2012).Crossref, Medline, CAS, Google Scholar
77 Cardenal F, Nadal E, Jove M, Faivre-Finn C. Concurrent systemic therapy with radiotherapy for the treatment of poor-risk patients with unresectable stage III non-small-cell lung cancer: a review of the literature. Ann. Oncol. 26(2), 278–288 (2015).Crossref, Medline, CAS, Google Scholar
78 Ottlakan A, Martucci N, Rocco G. Is surgery still the best management option for early stage NSCLC? Transl. Lung Cancer Res. 3(3), 159–163 (2014).Medline, Google Scholar
79 Cancer facts and figures 2013. www.cancer.org.Google Scholar
80 Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J. Clin. 64(1), 9–29 (2014).Crossref, Medline, Google Scholar
81 Alberts WM. The future and lung cancer: room for optimism? Cancer Control 7(1), 13–14 (2000).Crossref, Medline, CAS, Google Scholar
82 Hirsch FR, Jotte RM, Berry CA, Mencia WA, Stowell SA, Gardner AJ. Quality of care of patients with non-small-cell lung cancer: a report of a performance improvement initiative. Cancer Control 21(1), 90–97 (2014).Crossref, Medline, Google Scholar
83 Minuti G, D'incecco A, Cappuzzo F. Targeted therapy for NSCLC with driver mutations. Expert Opin. Biol. Ther. 13(10), 1401–1412 (2013).Crossref, Medline, CAS, Google Scholar
84 Perez-Soler R. Individualized therapy in non-small-cell lung cancer: future versus current clinical practice. Oncogene 28(Suppl. 1), S38–45 (2009).•• Provides good future perspectives of lung cancer therapy.Crossref, Medline, CAS, Google Scholar
85 Han JY, Kim SH, Lee YS et al. Comparison of targeted next-generation sequencing with conventional sequencing for predicting the responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in never-smokers with lung adenocarcinoma. Lung Cancer 85(2), 161–167 (2014).Crossref, Medline, Google Scholar
86 Ma J, Mannoor K, Gao L et al. Characterization of microRNA transcriptome in lung cancer by next-generation deep sequencing. Mol. Oncol. 8(7), 1208–1219 (2014).Crossref, Medline, CAS, Google Scholar
87 Yu H, Yuan J, Xiao C, Qin Y. Integrative genomic analyses of recepteur d'origine nantais and its prognostic value in cancer. Int. J. Mol. Med. 31(5), 1248–1254 (2013).Crossref, Medline, CAS, Google Scholar
88 Scoccianti C, Vesin A, Martel G et al. Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer: the EUELC cohort. Eur. Respir. J. 40(1), 177–184 (2012).Crossref, Medline, CAS, Google Scholar
89 Kuykendall A, Chiappori A. Advanced EGFR mutation-positive non-small-cell lung cancer: case report, literature review, and treatment recommendations. Cancer 21(1), 67–73 (2014).Google Scholar
90 Wigle DA. Biologic approaches to drug selection and targeted therapy: hype or clinical reality? Thorac. Surg. Clin. 23(3), 421–428 (2013).Crossref, Medline, Google Scholar
91 Morán T, Quiroga V, Gil MDL et al. Targeting EML4-ALK driven non-small cell lung cancer (NSCLC). Transl. Lung Cancer Res. 2(2), 128–141 (2013).Medline, CAS, Google Scholar
92 Li D, Ambrogio L, Shimamura T et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 27(34), 4702–4711 (2008).Crossref, Medline, CAS, Google Scholar
93 Kohler J, Schuler M. LUX-Lung 3: redundancy, toxicity or a major step forward? Afatinib as front-line therapy for patients with metastatic EGFR-mutated lung cancer. Future Oncol. 10(4), 533–540 (2014).•• Interesting recent clinical study report of EGFR mutated lung cancer treatment.Link, Google Scholar
94 Sozzi G, Boeri M. Potential biomarkers for lung cancer screening. Transl. Lung Cancer Res. 3(3), 139–148 (2014).Medline, CAS, Google Scholar
95 Zhu CQ, Tsao MS. Prognostic markers in lung cancer: is it ready for prime time? Transl. Lung Cancer Res. 3(3), 149–158 (2014).Medline, CAS, Google Scholar
96 Ruiz R, Hunis B, Raez LE. Immunotherapeutic Agents in Non-small-cell Lung Cancer Finally Coming to the Front Lines. Curr. Oncol. Rep. 16(9), 400 (2014).•• Discusses new and promising immunotherapy and possible agents that are in pipeline for lung cancer treatment.Crossref, Medline, Google Scholar
97 Szyszka-Barth K, Ramlau K, Gozdzik-Spychalska J et al. Actual status of therapeutic vaccination in non-small cell lung cancer. Contemp. Oncol. (Pozn.) 18(2), 77–84 (2014).• Discusses the limitation of vaccine/immunotherapy for lung cancer and how it is useful for only small set of population.Medline, CAS, Google Scholar
98 Seetharamu N. The state of the art in non-small cell lung cancer immunotherapy. Semin. Thorac. Cardiovasc. Surg. 26(1), 26–35 (2014).Crossref, Medline, Google Scholar
99 Thomas A, Jakopovic M. Immunotherapy for non-small-cell lung cancer. Expert Opin. Biol. Ther. 14(8), 1061–1064 (2014).Crossref, Medline, CAS, Google Scholar
100 Herrera ZM, Ramos TC. Pilot study of a novel combination of two therapeutic vaccines in advanced non-small-cell lung cancer patients. Cancer Immunol. Immunother. 63(7), 737–747 (2014).Crossref, Medline, CAS, Google Scholar
101 Alison MR, Lebrenne AC, Islam S. Stem cells and lung cancer: future therapeutic targets? Expert Opin. Biol. Ther. 9(9), 1127–1141 (2009).Crossref, Medline, CAS, Google Scholar
102 Hsu HS, Huang PI, Chang YL et al. Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer-derived CD133-positive cells. Cancer 117(13), 2970–2985 (2011).Crossref, Medline, CAS, Google Scholar
103 Nero TL, Morton CJ, Holien JK, Wielens J, Parker MW. Oncogenic protein interfaces: small molecules, big challenges. Nat. Rev. Cancer 14(4), 248–262 (2014).Crossref, Medline, CAS, Google Scholar
104 Liu G, Kelly WK, Wilding G, Leopold L, Brill K, Somer B. An open-label, multicenter, Phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin. Cancer Res. 15(9), 3172–3176 (2009).Crossref, Medline, CAS, Google Scholar
105 Mita AC, Denis LJ, Rowinsky EK et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin. Cancer Res. 15(2), 723–730 (2009).Crossref, Medline, CAS, Google Scholar
106 Kanthala S, Gauthier T, Satyanarayanajois S. Structure-activity relationships of peptidomimetics that inhibit PPI of HER2–HER3. Biopolymers 101(6), 693–702 (2014).Crossref, Medline, CAS, Google Scholar
107 Banappagari S, Ronald S, Satyanarayanajois SD. Structure-activity relationship of conformationally constrained peptidomimetics for antiproliferative activity in HER2-overexpressing breast cancer cell lines. MedChemComm 2(8), 752–759 (2011).Crossref, Medline, CAS, Google Scholar
108 Banappagari S, Corti M, Pincus S, Satyanarayanajois S. Inhibition of protein-protein interaction of HER2–EGFR and HER2–HER3 by a rationally designed peptidomimetic. J. Biomol. Str. Dyn. 30(5), 594–606 (2012).Crossref, Medline, CAS, Google Scholar
109 Banappagari S, Ronald S, Satyanarayanajois SD. A conformationally constrained peptidomimetic binds to the extracellular region of HER2 protein. J. Biomol. Str. Dyn. 28(3), 289–308 (2010).Crossref, Medline, CAS, Google Scholar
110 Lu C, Mi LZ, Grey MJ et al. Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor. Mol. Cell Biol. 30(22), 5432–5443 (2010).Crossref, Medline, CAS, Google Scholar
111 Fisher RD, Ultsch M, Lingel A et al. Structure of the complex between HER2 and an antibody paratope formed by side chains from tryptophan and serine. J. Mol. Biol. 402(1), 217–229 (2010).Crossref, Medline, CAS, Google Scholar

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This project was supported by an Institutional Development Award from the National Institute of General Medical Sciences of the NIH under grant number 8P20GM103424. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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