Mayo C, Bertran-Alamillo J, Molina-Vila MA, Gimenez-Capitan A, Costa C, Rosell R. Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications. Pharmacogenomics. 2012;13:789–802.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.
Chi A, Remick S, Tse W. EGFR inhibition in non–small cell lung cancer: current evidence and future directions. Biomark Res. 2013;1:2.
Dziadziuszko R, Jassem J. Epidermal growth factor receptor (EGFR) inhibitors and derived treatments. Ann Oncol. 2012;23:x193–6.
Heuckmann JM, Rauh D, Thomas RK. Epidermal growth factor receptor (EGFR) signaling and covalent EGFR inhibition in lung cancer. J Clin Oncol. 2012;30:3417–20.
Rossi A. Cetuximab and non–small-cell lung cancer: end of the story? Lancet Oncol. 2013;14:1251–3.
Berger C, Madshus IH, Stang E. Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis. Exp Cell Res. 2012;318:2578–91.
Bareschino MA, Schettino C, Troiani T, Martinelli E, Morgillo F, Ciardiello F. Erlotinib in cancer treatment. Ann Oncol. 2007;18:vi35–41.
Passaro A, Alesini D, Pochesci A, Cortesi E. Erlotinib and gefitinib for elderly patients with advanced non–small-cell lung cancer. Anticancer Agents Med Chem. 2014;14:646–50.
Yang X, Yang K, Kuang K. The efficacy and safety of EGFR inhibitor monotherapy in non–small cell lung cancer: a systematic review. Curr Oncol Rep. 2014;16:390.
Douillard JY, Pirker R, O’Byrne KJ, Kerr KM, Storkel S, Von Heydebreck A, et al. Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non–small-cell lung cancer. J Thorac Oncol. 2014;9:717–24.
Shigeta K, Hayashida T, Hoshino Y, Okabayashi K, Endo T, Ishii Y, et al. Expression of epidermal growth factor receptor detected by cetuximab indicates its efficacy to inhibit and proliferation of colorectal cancer cells. PLoS One. 2013;8:e66302.
Pirker R. EGFR-directed monoclonal antibodies in non–small cell lung cancer. Target Oncol. 2013;8:47–53.
Wang Y, Schmid-Bindert G, Zhou C. Erlotinib in the treatment of advanced non–small cell lung cancer: an update for clinicians. Ther Adv Med Oncol. 2012;4:19–29.
Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66:3992–5.
Califano R, Landi L, Cappuzzo F. Prognostic and predictive value of K-RAS mutations in non–small cell lung cancer. Drugs. 2012;72:28–36.
Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2:e17.
Hynes NE, MacDonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009;21:177–84.
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141:1117–34.
Lim WA, Pawson T. Phosphotyrosine signaling: evolving a new cellular communication system. Cell. 2010;142:661–7.
Schneider MR, Wolf E. The epidermal growth factor receptor ligands at a glance. J Cell Physio. 2009;218:460–6.
Logue JS, Morrison DK. Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. Genes Dev. 2012;26:641–50.
Singh AB, Harris RC. Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal. 2005;17:1183–93.
Arkhipov A, Shan Y, Das R, Endres NF, Eastwood MP, Wemmer DE, et al. Architecture and membrane interactions of the EGF receptor. Cell. 2013;152:557–69.
Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–37.
Hunter T. Tyrosine phosphorylation: thirty years and counting. Curr Opin Cell Biol. 2009;21:140–6.
Pawson T. Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell. 2004;116:191–203.
Pawson T, Nash P. Assembly of cell regulatory systems through protein interaction domains. Science. 2003;300:445–52.
Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7:505–16.
Molina JR, Adjei AA. The Ras/Raf/MAPK pathway. J Thorac Oncol. 2006;1:7–9.
Chen Y, Wang BC, Xiao Y. PI3K: a potential therapeutic target for cancer. J Cell Physio. 2012;227:2818–21.
Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9:59–71.
Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283–96.
Quesnelle KM, Boehm AL, Grandis JR. STAT-mediated EGFR signaling in cancer. J Cell Biochem. 2007;102:311–9.
Gazdar AF. Personalized medicine and inhibition of EGFR signaling in lung cancer. N Engl J Med. 2009;361:1018–20.
Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7:169–81.
Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004;64:8919–23.
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;366:2–16.
Alarcon T, Page KM. Stochastic models of receptor oligomerization by bivalent ligand. J R Soc Interface. 2006;3:545–59.
Solca F, Dahl G, Zoephel A, Bader G, Sanderson M, Klein C, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharm Exp Ther. 2012;343:342–50.
Lim SH, Lee JY, Sun JM, Ahn JS, Park K, Ahn MJ. Comparison of clinical outcomes following gefitinib and erlotinib treatment in non–small-cell lung cancer patients harboring an epidermal growth factor receptor mutation in either exon 19 or 21. J Thorac Oncol. 2014;9:506–11.
Bronte G, Rolfo C, Giovannetti E, Cicero G, Pauwels P, Passiglia F, et al. Are erlotinib and gefitinib interchangeable, opposite or complementary for non–small cell lung cancer treatment? Biological, pharmacological and clinical aspects. Crit Rev Oncol Hemat. 2014;89:300–13.
Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, et al. Erlotinib as maintenance treatment in advanced non–small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010;11:521–9.
Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, et al. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non–small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012;30:3002–11.
Lee KH, Lee KY, Jeon YJ, Jung MH, Son C, Lee MK, et al. Gefitinib in selected patients with pre-treated non–small-cell lung cancer: results from a phase IV, multicenter, non-randomized study (SELINE). Tuberc Respir Dis. 2012;73:303–11.
Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009;361:958–67.
Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 2006;12:6494–501.
Engelman JA, Settleman J. Acquired resistance to tyrosine kinase inhibitors during cancer therapy. Curr Opin Genet Dev. 2008;18:73–9.
Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005;2:e73.
Nebhan C, Pao W. Further advances in genetically informed lung cancer medicine. J Thorac Oncol. 2013;8:521–2.
Pao W, Iafrate AJ, Su Z. Genetically informed lung cancer medicine. J Pathol. 2011;223:230–40.
Keating GM. Afatinib: a review of its use in the treatment of advanced non–small cell lung cancer. Drugs. 2014;74:207–21.
Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4:1046–61.
Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27:4702–11.
Engelman JA, Zejnullahu K, Gale CM, Lifshits E, Gonzales AJ, Shimamura T, et al. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007;67:11924–32.
Costa DB, Kobayashi S, Tenen DG, Huberman MS. Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non–small cell lung cancers. Lung Cancer. 2007;58:95–103.
Kobayashi T, Koizumi T, Agatsuma T, Yasuo M, Tsushima K, Kubo K, et al. A phase II trial of erlotinib in patients with EGFR wild-type advanced non–small-cell lung cancer. Cancer Chemother Pharm. 2012;69:1241–6.
Pao W, Girard N. New driver mutations in non–small-cell lung cancer. Lancet Oncol. 2011;12:175–80.
Baty F, Rothschild S, Fruh M, Betticher D, Droge C, Cathomas R, et al. EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non–small cell lung cancer. PLoS One. 2013;8:e72966.
Pirker R, Pereira JR, Szczesna A, Von Pawel J, Krzakowski M, Ramlau R, et al. Cetuximab plus chemotherapy in patients with advanced non–small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet Oncol. 2009;373:1525–31.
Pirker R, Pereira JR, Von Pawel J, Krzakowski M, Ramlau R, Park K, 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. 2012;13:33–42.
Khambata-Ford S, Harbison C, Woytowitz D, Awad M, Horak C, Xu LA, et al. K-Ras mutation (mut), EGFR-related, and exploratory markers as response predictors of cetuximab in first-line advanced NSCLC: Retrospective analyses of the BMS099 trial. J Clin Oncol. (Meeting Abstracts) 2009;27:no.15S: 8021.
Khambata-Ford S, Harbison CT, Hart LL, Awad M, Xu LA, Horak CE, et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non–small-cell lung cancer. J Clin Oncol. 2010;28:918–27.
Kim ES, Neubauer M, Cohn A, Schwartzberg L, Garbo L, Caton J, et al. Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non–small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. Lancet Oncol. 2013;14:1326–36.
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.
Zhu CQ, Da Cunha SG, Ding K, Sakurada A, Cutz JC, Liu N, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol. 2008;26:4268–75.
Garassino MC, Marabese M, Rusconi P, Rulli E, Martelli O, Farina G, et al. Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non–small-cell lung cancer. Ann Oncol. 2011;22:235–7.
Maus MKH, Grimminger PP, Mack PC, Astrow SH, Stephens C, Zeger G, et al. KRAS mutations in non–small-cell lung cancer and colorectal cancer: implications for EGFR-targeted therapies. Lung Cancer. 2014;83:163–7.
Ferte C, Besse B, Dansin E, Parent F, Buisine MP, Copin MC, et al. Durable responses to Erlotinib despite KRAS mutations in two patients with metastatic lung adenocarcinoma. Ann Oncol. 2010;21:1385–7.
Danenberg KD, Grimminger PP, Mack PC, Danenberg PV, Cooc J, Stephens C, et al. KRAS mutations (MTs) in non–small cell lung cancer (NSCLC) versus colorectal cancer (CRC): implications for cetuximab therapy. J Clin Oncol. 2010;28:10529.
Santini D, Loupakis F, Vincenzi B, Floriani I, Stasi I, Canestrari E, et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist. 2008;13:1270–5.
Wang L, Hu H, Pan Y, Wang R, Li Y, Shen L, et al. PIK3CA mutations frequently coexist with EGFR/KRAS mutations in non–small cell lung cancer and suggest poor prognosis in EGFR/KRAS wildtype subgroup. PLoS One. 2014;9:e88291.
Zimmermann S, Peters S. Going beyond EGFR. Ann Oncol. 2012;23:197–203.
Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non–small-cell lung cancer. Nat Rev Cancer. 2010;10:760–74.
Bader AG, Kang S, Vogt PK. Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci U S A. 2006;103:1475–9.
Engelman JA, Mukohara T, Zejnullahu K, Lifshits E, Borras AM, Gale CM, et al. Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer. J Clin Invest. 2006;116:2695–706.
De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.
D’Amato V, Rosa R, D’Amato C, Formisano L, Marciano R, Nappi L, et al. The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models. Br J Cancer. 2014;110:2887–95.
Rebucci M, Peixoto P, Dewitte A, Wattez N, De Nuncques MA, Rezvoy N, et al. Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance. Int J Oncol. 2011;38:189–200.
Sos ML, Koker M, Weir BA, Heynck S, Rabinovsky R, Zander T, et al. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res. 2009;69:3256–61.
Endoh H, Yatabe Y, Kosaka T, Kuwano H, Mitsudomi T. PTEN and PIK3CA expression is associated with prolonged survival after gefitinib treatment in EGFR-mutated lung cancer patients. J Thorac Oncol. 2006;1:629–34.
Kim SM, Kim JS, Kim JH, Yun CO, Kim EM, Kim HK, et al. Acquired resistance to cetuximab is mediated by increased PTEN instability and leads cross-resistance to gefitinib in HCC827 NSCLC cells. Cancer Lett. 2010;296:150–9.
Mao C, Liao RY, Chen Q. Loss of PTEN expression predicts resistance to EGFR-targeted monoclonal antibodies in patients with metastatic colorectal cancer. Br J Cancer. 2010;102:940.
Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009;27:5924–30.
Furukawa M, Soh J, Yamamoto H, Ichimura K, Shien K, Maki Y, et al. Silenced expression of NFKBIA in lung adenocarcinoma patients with a never-smoking history. Acta Med Okayama. 2013;67:19–24.
Jacobs MD, Harrison SC. Structure of an IkappaBalpha/NF-kappaB complex. Cell. 1998;95:749–58.
Bivona TG, Hieronymus H, Parker J, Chang K, Taron M, Rosell R, et al. FAS and NF-kappaB signalling modulate dependence of lung cancers on mutant EGFR. Nature. 2011;471:523–6.
Scartozzi M, Bearzi I, Pierantoni C, Mandolesi A, Loupakis F, Zaniboni A, et al. Nuclear factor-kappaB tumor expression predicts response and survival in irinotecan-refractory metastatic colorectal cancer treated with cetuximab-irinotecan therapy. J Clin Oncol. 2007;25:3930–5.
Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene. 2000;19:5548–57.
Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11:834–48.
Sadiq AA, Salgia R. MET as a possible target for non–small-cell lung cancer. J Clin Oncol. 2013;31:1089–96.
Park S, Choi YL, Sung CO, An J, Seo J, Ahn MJ, et al. High MET copy number and MET overexpression: poor outcome in non–small cell lung cancer patients. Histol Histopathol. 2012;27:197–207.
Lutterbach B, Zeng Q, Davis LJ, Hatch H, Hang G, Kohl NE, et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res. 2007;67:2081–8.
Yano S, Wang W, Li Q, Matsumoto K, Sakurama H, Nakamura T, et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res. 2008;68:9479–87.
Sgambato A, Casaluce F, Maione P, Rossi A, Rossi E, Napolitano A, et al. The c-Met inhibitors: a new class of drugs in the battle against advanced non–small-cell lung cancer. Curr Pharm Des. 2012;18:6155–68.
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 U S A. 2007;104:20932–7.
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;316:1039–43.
Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G, et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov. 2013;3:658–73.
Song N, Liu S, Zhang J, Liu J, Xu L, Liu Y, et al. Cetuximab-induced MET activation acts as a novel resistance mechanism in colon cancer cells. Int J Mol Sci. 2014;15:5838–51.
Jain A, Penuel E, Mink S, Schmidt J, Hodge A, Favero K, et al. HER kinase axis receptor dimer partner switching occurs in response to EGFR tyrosine kinase inhibition despite failure to block cellular proliferation. Cancer Res. 2010;70:1989–99.
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;27:3944–56.
Pinkas-Kramarski R, Soussan L, Waterman H, Levkowitz G, Alroy I, Klapper L, et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J. 1996;15:2452–67.
Garrido-Castro AC, Felip E. HER2 driven non–small cell lung cancer (NSCLC): potential therapeutic approaches. Transl Cancer Res. 2013;2:122–7.
Martin V, Landi L, Molinari F, Fountzilas G, Geva R, Riva A, et al. HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. Br J Cancer. 2013;108:668–75.
Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, Giri U, et al. Increased VEGFR-2 gene copy is associated with chemoresistance and shorter survival in patients with non–small-cell lung carcinoma who receive adjuvant chemotherapy. Cancer Res. 2011;71:5512–21.
Gadgeel SM, Chen W, Cote ML, Bollig-Fischer A, Land S, Schwartz AG, et al. Fibroblast growth factor receptor 1 amplification in non–small cell lung cancer by quantitative real-time PCR. PLoS One. 2013;8:e79820.
Donnem T, Al-Saad S, Al-Shibli K, Andersen S, Busund LT, Bremnes RM. Prognostic impact of platelet-derived growth factors in non–small cell lung cancer tumor and stromal cells. J Thorac Oncol. 2008;3:963–70.
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.
Ludovini V, Flacco A, Bianconi F, Ragusa M, Vannucci J, Bellezza G, et al. Concomitant high gene copy number and protein overexpression of IGF1R and EGFR negatively affect disease-free survival of surgically resected non–small-cell-lung cancer patients. Cancer Chemother Pharm. 2013;71:671–80.
Carter CA, Giaccone G. Treatment of nonsmall cell lung cancer: overcoming the resistance to epidermal growth factor receptor inhibitors. Curr Opin Oncol. 2012;24:123–9.
Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, et al. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non–small-cell lung cancer. Clin Lung Cancer. 2012;13:391–5.
Chong CR, Janne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med. 2013;19:1389–400.
Rolfo C, Giovannetti E, Hong DS, Bivona T, Raez LE, Bronte G, et al. Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. Cancer Treat Rev. 2014;40:990–1004.
Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, et al. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol. 2009;20:84–90.
Engelman JA, Janne PA, Mermel C, Pearlberg J, Mukohara T, Fleet C, et al. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non–small cell lung cancer cell lines. Proc Natl Acad Sci U S A. 2005;102:3788–93.