Skip to main content

Advertisement

SpringerLink
Log in

Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non–small lung cancer with EGFR TKIs-resistant mutation

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Previous studies have demonstrated that sunitinib has the anti-tumor activity in human non–small cell lung cancer (NSCLC). This study was aimed to investigate the efficacy of single use of sunitinib and that of concurrent or sequential administration of sunitinib and docetaxel in NSCLC cell lines that are resistant to EGFR TKIs.

Methods

NSCLC cell lines with EGFR T790M mutation and K-ras mutation were exposed to either sunitinib or docetaxel or both based on various sequential administrations. After exposure, the cell viability was measured by MTT assay, cell cycle distribution was analyzed by flow cytometry, and alterations in signaling pathway were determined by immunoblotting.

Results

Sunitinib exhibited dose-dependent growth inhibition in NSCLC cell lines and arrested cell cycle at G1 phase, whereas docetaxel arrested at S phase. Although single or concurrent use of sunitinib and docetaxel has some anti-proliferative effects, the sequential administrations of both drugs remarkably enhanced anti-tumor activity. When cells were exposed to docetaxel followed by sunitinib, synergism was observed. The molecular basis of this synergism is that the signaling pathways that were initially activated by docetaxel exposure were efficiently suppressed by the subsequent exposure to sunitinib. In contrast, the reverse of this sequential administration resulted in antagonism, which may be due to differential effects on cell cycle arrest.

Conclusions

Sunitinib as a single agent exhibits anti-proliferative effects in vitro in NSCLC cell lines with EGFR T790M and K-ras mutations but the sequential administration of docetaxel followed by sunitinib is superior to sunitinib followed by docetaxel and concurrent administration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM (2003) SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2:471–478

    PubMed  CAS  Google Scholar 

  • Albain KS, Green SJ, Ravdin PM, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Schneider DJ, Abeloff MD, Norton L, Henderson IC, Lew D, Livingston RB, Martino S, Osborne CK (2002) Adjuvant chemohormonal therapy for primary breast cancer should be sequential instead of concurrent: initial results from intergroup trial 0100 (SWOG-8814) [abstract 143]. Proc Am Soc Clin Oncol 21:37a

    Google Scholar 

  • Ardizzoni A, Tiseo M (2004) Second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). J Chemother 16(Suppl 4):104–107

    PubMed  CAS  Google Scholar 

  • Aviel-Ronen S, Blackhall FH, Shepherd FA, Tsao MS (2006) K-ras mutations in non-small-cell lung carcinoma: a review. Clin Lung Cancer 8:30–38

    Article  PubMed  CAS  Google Scholar 

  • Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R, Sharma SV, Brannigan BW, Mohapatra G, Settleman J, Haber DA (2005) Inherited susceptibility to lung cancer may be associated with the T790 M drug resistance mutation in EGFR. Nat Genet 37:1315–1316

    Article  PubMed  CAS  Google Scholar 

  • Cheng H, An SJ, Zhang XC, Dong S, Zhang YF, Chen ZH, Chen HJ, Guo AL, Lin QX, Wu YL (2011) In vitro sequence-dependent synergism between paclitaxel and gefitinib in human lung cancer cell lines. Cancer Chemother Pharmacol 67:637–646

    Article  PubMed  CAS  Google Scholar 

  • Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27–55

    Article  PubMed  CAS  Google Scholar 

  • Chow LQ, Eckhardt SG (2007) Sunitinib: from rational design to clinical efficacy. J Clin Oncol 25:884–896

    Article  PubMed  CAS  Google Scholar 

  • Clarke SJ, Rivory LP (1999) Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet 36:99–114

    Article  PubMed  CAS  Google Scholar 

  • D’Addario G, Pintilie M, Leighl NB, Feld R, Cerny T, Shepherd FA (2005) Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol 23:2926–2936

    Article  PubMed  Google Scholar 

  • Davies AM, Ho C, Lara PN Jr, Mack P, Gumerlock PH, Gandara DR (2006) Pharmacodynamic separation of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy in non-small-cell lung cancer. Clin Lung Cancer 7:385–388

    Article  PubMed  CAS  Google Scholar 

  • de Boüard S, Herlin P, Christensen JG, Lemoisson E, Gauduchon P, Raymond E, Guillamo JS (2007) Antiangiogenic and anti-invasive effects of sunitinib on experimental human glioblastoma. Neuro Oncol 9:412–423

    Article  PubMed  Google Scholar 

  • Donnem T, Al-Saad S, Al-Shibli K, Busund LT, Bremnes RM (2010) Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer. Ann Oncol 21:223–231

    Article  PubMed  CAS  Google Scholar 

  • Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Jänne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23:5900–5909

    Article  PubMed  CAS  Google Scholar 

  • Faivre S, Delbaldo C, Vera K, Robert C, Lozahic S, Lassau N, Bello C, Deprimo S, Brega N, Massimini G, Armand JP, Scigalla P, Raymond E (2006) Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24:25–35

    Article  PubMed  CAS  Google Scholar 

  • Faivre S, Demetri G, Sargent W, Raymond E (2007) Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov 6:734–745

    Article  PubMed  CAS  Google Scholar 

  • Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong RP, Baselga J (2003) Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol 21:2237–2246

    Article  PubMed  CAS  Google Scholar 

  • Furugaki K, Iwai T, Shirane M, Kondoh K, Moriya Y, Mori K (2010) Schedule-dependent antitumor activity of the combination with erlotinib and docetaxel in human non-small cell lung cancer cells with EGFR mutation, KRAS mutation or both wild-type EGFR and KRAS. Oncol Rep 24:1141–1146

    Article  PubMed  CAS  Google Scholar 

  • Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J (2007) Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 25:1545–1552

    Article  PubMed  CAS  Google Scholar 

  • Gazdar AF (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28(Suppl 1):S24–S31

    Article  PubMed  CAS  Google Scholar 

  • Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, Von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH (2004) Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 1. J Clin Oncol 22:777–784

    Article  PubMed  CAS  Google Scholar 

  • Gligorov J, Lotz JP (2004) Preclinical pharmacology of the taxanes: implications of the differences. Oncologist 9(Suppl 2):3–8

    Article  PubMed  CAS  Google Scholar 

  • Gloeckler Ries LA, Reichman ME, Lewis DR, Hankey BF, Edwards BK (2003) Cancer survival and incidence from the Surveillance, Epidemiology, and End Results (SEER) program. Oncologist 8:541–552

    Article  PubMed  Google Scholar 

  • Goodman VL, Rock EP, Dagher R, Ramchandani RP, Abraham S, Gobburu JV, Booth BP, Verbois SL, Morse DE, Liang CY, Chidambaram N, Jiang JX, Tang S, Mahjoob K, Justice R, Pazdur R (2007) Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res 13:1367–1373

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  PubMed  CAS  Google Scholar 

  • Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22:1589–1597

    Article  PubMed  CAS  Google Scholar 

  • Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH (2004) Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 2. J Clin Oncol 22:785–794

    Article  PubMed  CAS  Google Scholar 

  • Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA (2005) TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23:5892–5899

    Article  PubMed  CAS  Google Scholar 

  • Hui EP, Lui VW, Wong CS, Ma BB, Lau CP, Cheung CS, Ho K, Cheng SH, Ng MH, Chan AT (2010) Preclinical evaluation of sunitinib as single agent or in combination with chemotherapy in nasopharyngeal carcinoma. Invest New Drugs. doi:10.1007/s10637-010-9451-1

  • Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  • Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352:786–792

    Article  PubMed  CAS  Google Scholar 

  • Koukourakis MI, Giatromanolaki A, O’Byrne KJ, Comley M, Whitehouse RM, Talbot DC, Gatter KC, Harris AL (1997) Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small-cell lung cancer. Br J Cancer 75:477–481

    Article  PubMed  CAS  Google Scholar 

  • Li T, Ling YH, Goldman ID, Perez-Soler R (2007) Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non-small cell lung cancer cells. Clin Cancer Res 13:3413–3422

    Article  PubMed  CAS  Google Scholar 

  • Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  PubMed  CAS  Google Scholar 

  • Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388

    Article  PubMed  CAS  Google Scholar 

  • Mahaffey CM, Davies AM, Lara PN Jr, Pryde B, Holland W, Mack PC, Gumerlock PH, Gandara DR (2007) Schedule-dependent apoptosis in K-ras mutant non-small-cell lung cancer cell lines treated with docetaxel and erlotinib: rationale for pharmacodynamic separation. Clin Lung Cancer 8:548–553

    Article  PubMed  CAS  Google Scholar 

  • Masago K, Fujita S, Togashi Y, Kim YH, Hatachi Y, Fukuhara A, Nagai H, Sakamori Y, Mio T, Mishima M (2011) Clinicopathologic factors affecting the progression-free survival of patients with advanced non-small-cell lung cancer after gefitinib therapy. Clin Lung Cancer 12:56–61

    Article  PubMed  Google Scholar 

  • Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, Schreck RE, Abrams TJ, Ngai TJ, Lee LB, Murray LJ, Carver J, Chan E, Moss KG, Haznedar JO, Sukbuntherng J, Blake RA, Sun L, Tang C, Miller T, Shirazian S, McMahon G, Cherrington JM (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9:327–337

    PubMed  CAS  Google Scholar 

  • Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957

    Article  PubMed  CAS  Google Scholar 

  • Montero A, Fossella F, Hortobagyi G, Valero V (2005) Docetaxel for treatment of solid tumours: a systematic review of clinical data. Lancet Oncol 6:229–239

    Article  PubMed  CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  PubMed  CAS  Google Scholar 

  • O’Byrne KJ, Koukourakis MI, Giatromanolaki A, Cox G, Turley H, Steward WP, Gatter K, Harris AL (2000) Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer 82:1427–1432

    PubMed  Google Scholar 

  • O’Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM (2003) SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101:3597–3605

    Article  PubMed  Google Scholar 

  • Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  PubMed  CAS  Google Scholar 

  • Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H (2005a) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2:e73

    Article  PubMed  Google Scholar 

  • Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG, Varmus HE (2005b) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2:e17

    Article  PubMed  Google Scholar 

  • Pfizer Inc (2010) Pfizer reports Progression-Free survival in SUN 1087 combination trial of sunitinib with erlotinib for NSCLC. IOP Publishing news-medical. http://www.news-medical.net/news/20100824/Pfizer-reports-Progression-Free-survival-in-SUN-1087-combination-trial-of-sunitinib-with-erlotinib-for-NSCLC.aspx. Accessed 24 Aug 2010

  • Polyzos A (2008) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors. J Steroid Biochem Mol Bio 108:261–266

    Article  CAS  Google Scholar 

  • Prenen H, Cools J, Mentens N, Folens C, Sciot R, Schöffski P, Van Oosterom A, Marynen P, Debiec-Rychter M (2006) Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res 12:2622–2627

    Article  PubMed  CAS  Google Scholar 

  • Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27:1227–1234

    Article  PubMed  CAS  Google Scholar 

  • Reck M, Frickhofen N, Cedres S, Gatzemeier U, Heigener D, Fuhr HG, Thall A, Lanzalone S, Stephenson P, Ruiz-Garcia A, Chao R, Felip E (2010) Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: a phase I dose-escalation study. Lung Cancer 70:180–187

    Article  PubMed  Google Scholar 

  • Riely GJ, Pao W, Pham D, Li AR, Rizvi N, Venkatraman ES, Zakowski MF, Kris MG, Ladanyi M, Miller VA (2006) Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 12:839–844

    Article  PubMed  CAS  Google Scholar 

  • Robert F, Sandler A, Schiller JH, Liu G, Harper K, Verkh L, Huang X, Ilagan J, Tye L, Chao R, Traynor AM (2010) Sunitinib in combination with docetaxel in patients with advanced solid tumors: a phase I dose-escalation study. Cancer Chemother Pharmacol 66:669–680

    Article  PubMed  CAS  Google Scholar 

  • Saigal B, Glisson BS, Johnson FM (2008) Dose-dependent and sequence-dependent cytotoxicity of erlotinib and docetaxel in head and neck squamous cell carcinoma. Anticancer Drugs 19:465–475

    Article  PubMed  CAS  Google Scholar 

  • Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  PubMed  CAS  Google Scholar 

  • Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132

    Article  PubMed  CAS  Google Scholar 

  • Shikada Y, Yonemitsu Y, Koga T, Onimaru M, Nakano T, Okano S, Sata S, Nakagawa K, Yoshino I, Maehara Y, Sueishi K (2005) Platelet-derived growth factor-AA is an essential and autocrine regulator of vascular endothelial growth factor expression in non-small cell lung carcinomas. Cancer Res 65:7241–7248

    Article  PubMed  CAS  Google Scholar 

  • Socinski MA, Novello S, Brahmer JR, Rosell R, Sanchez JM, Belani CP, Govindan R, Atkins JN, Gillenwater HH, Pallares C, Tye L, Selaru P, Chao RC, Scagliotti GV (2008) Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol 26:650–656

    Article  PubMed  CAS  Google Scholar 

  • Socinski MA, Scappaticci FA, Samant M, Kolb MM, Kozloff MF (2010) Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer. J Thorac Oncol 5:354–360

    Article  PubMed  Google Scholar 

  • Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR (2005) Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65:7052–7058

    Article  PubMed  CAS  Google Scholar 

  • Sundberg C, Ljungström M, Lindmark G, Gerdin B, Rubin K (1993) Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma. Am J Pathol 143:1377–1388

    PubMed  CAS  Google Scholar 

  • Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A, Okinaga S, Nagashima M, Oizumi S, Uematsu K, Nagai Y, Moriyama G, Miyazawa H, Ikebuchi K, Morita S, Kobayashi K, Hagiwara K (2010) Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 126:651–655

    Article  PubMed  CAS  Google Scholar 

  • Torres K, Horwitz SB (1998) Mechanisms of taxol-induced cell death are concentration dependent. Cancer Res 58:3620–3626

    PubMed  CAS  Google Scholar 

  • Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha Santos G, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA (2005) Erlotinib in lung cancer-molecular and clinical predictors of outcome. N Engl J Med 353:133–144

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Gout I, Proud CG (2001) Cross-talk between the ERK and p70 S6 kinase (S6K) signaling pathways. MEK-dependent activation of S6K2 in cardiomyocytes. J Biol Chem 276:32670–32677

    Article  PubMed  CAS  Google Scholar 

  • Yacoub A, Han SI, Caron R, Gilfor D, Mooberry S, Grant S, Dent P (2003) Sequence dependent exposure of mammary carcinoma cells to Taxotere and the MEK1/2 inhibitor U0126 causes enhanced cell killing in vitro. Cancer Biol Ther 2:670–676

    PubMed  CAS  Google Scholar 

  • Yokoyama T, Kondo M, Goto Y, Fukui T, Yoshioka H, Yokoi K, Osada H, Imaizumi K, Hasegawa Y, Shimokata K, Sekido Y (2006) EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification. Cancer Sci 97:753–759

    Article  PubMed  CAS  Google Scholar 

  • Yoon CY, Lee JS, Kim BS, Jeong SJ, Hong SK, Byun SS, Lee SE (2011) Sunitinib malate synergistically potentiates anti-tumor effect of gemcitabine in human bladder cancer cells. Korean J Urol 52:55–63

    Article  PubMed  Google Scholar 

  • Yuan A, Yu CJ, Kuo SH, Chen WJ, Lin FY, Luh KT, Yang PC, Lee YC (2001) Vascular endothelial growth factor 189 mRNA isoform expression specifically correlates with tumor angiogenesis, patient survival, and postoperative relapse in non-small-cell lung cancer. J Clin Oncol 19:432–441

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was granted by Anhui Provincial Science and Technology Agency Foundation of China (No. 07020304102) and supported by Guangdong Lung Cancer institute, Guangdong Academy of Medical Sciences. We thank Dr. Hongxia Tian for FACS analysis.

Conflict of interest

The authors declare no potential conflict of interest.

Author information

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Anhui Medical University, No. 218, Ji Xi Road, Hefei, 230022, China

    Feng Pan & Yueyin Pan

  2. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, No. 81, Mei Shan Road, Hefei, 230032, China

    Jing Tian

  3. Guangdong Lung Cancer Institute, Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, No. 106, Zhong Shan 2nd Road, Guangzhou, 510080, China

    Xuchao Zhang

  4. Department of Geriatrics, The Third Affiliated Hospital of Anhui Medical University, No. 390, Huai He Road, Hefei, 230061, China

    Ying Zhang

Authors
  1. Feng Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jing Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuchao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yueyin Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ying Zhang or Yueyin Pan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pan, F., Tian, J., Zhang, X. et al. Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non–small lung cancer with EGFR TKIs-resistant mutation. J Cancer Res Clin Oncol 137, 1397–1408 (2011). https://doi.org/10.1007/s00432-011-1009-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-011-1009-x

Keywords

Search

Navigation