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Review Article

ErbB Receptors as Prognostic and Therapeutic Drug Targets in Bone and Soft Tissue Sarcomas

, , , , &
Pages 533-542 | Received 19 Feb 2014, Accepted 08 Sep 2014, Published online: 27 Oct 2014

REFERENCES

  • Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341–354.
  • Hynes NE, MacDonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol 2009;21:177–184.
  • Tebbutt N, Pedersen MW, Johns TG. Targeting the ERBB family in cancer: couples therapy. Nat Rev Cancer 2013;13:663–673.
  • Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783–1791.
  • Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus Docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008;372:1809–1818.
  • Shmookler B, Bickels J, Jelinek J, Sugarbaker P, Malawer MM. Bone and soft-tissue sarcomas: epidemiology, radiology, pathology and fundamentals of surgical treatment.
  • Holbro T, Hynes NE. ErbB receptors: directing key signaling networks throughout life. Annu Rev Pharmacol Toxicol 2004;44:195–217.
  • Prenzel N, Fischer OM, Streit S, Hart S, Ullrich A. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer 2001;8:11–31.
  • Roskoski R, Jr. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacol Res 2014;79:34–74.
  • Zhang Q, Park E, Kani K, Landgraf R. Functional isolation of activated and unilaterally phosphorylated heterodimers of ERBB2 and ERBB3 as scaffolds in ligand-dependent signaling. Proc Natl Acad Sci USA 2012;109:13237–13242.
  • Graus-Porta D, Beerli RR, Daly JM, Hynes NE. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J;199716:1647–1655.
  • Sasaki T, Hiroki K, Yamashita Y. The role of epidermal growth factor receptor in cancer metastasis and microenvironment. Biomed Res Int 2013;2013:546318.
  • Tsujioka H, Yotsumoto F, Shirota K, Horiuchi S, Yoshizato T, Kuroki M, Miyamoto S. Emerging strategies for ErbB ligand-based targeted therapy for cancer. Anticancer Res 2010;30:3107–3112.
  • Groenen LC, Nice EC, Burgess AW. Structure–function relationships for the EGF/TGF-alpha family of mitogens. Growth Factors 1994;11:235–257.
  • Toyoda H, Komurasaki T, Uchida D, Takayama Y, Isobe T, Okuyama T, Hanada K. Epiregulin. A novel epidermal growth factor with mitogenic activity for rat primary hepatocytes. J Biol Chem 1995;270:7495–7500.
  • Higashiyama S, Iwabuki H, Morimoto C, Hieda M, Inoue H, Matsushita N. Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands. Cancer Sci 2008;99:214–220.
  • Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001;2:127–137.
  • Schlessinger J. Common and distinct elements in cellular signaling via EGF and FGF receptors. Science 2004;306:1506–1507.
  • Yu H, Jove R. The STATs of cancer—new molecular targets come of age. Nat Rev Cancer 2004;4:97–105.
  • Eccles SA. The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. Int J Dev Biol 2011;55:685–696.
  • Schulze WX, Deng L, Mann M. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol 2005;1:0008.
  • Huang MH, Lee JH, Chang YJ, Tsai HH, Lin YL, Lin AM, Yang JC. MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to Gefitinib. Mol Oncol 2013;7:112–120.
  • Turke AB, Song Y, Costa C, Cook R, Arteaga CL, Asara JM, Engelman JA. MEK inhibition leads to PI3K/AKT activation by relieving a negative feedback on ERBB receptors. Cancer Res 2012;72:3228–3237.
  • Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer 2009;115:1531–1543.
  • Chou AJ, Gorlick R. Chemotherapy resistance in osteosarcoma: current challenges and future directions. Expert Rev Anticancer Ther 2006;6:1075–1085.
  • Oda Y, Wehrmann B, Radig K, Walter H, Rose I, Neumann W, Roessner A. Expression of growth factors and their receptors in human osteosarcomas. Immunohistochemical detection of epidermal growth factor, platelet-derived growth factor and their receptors: its correlation with proliferating activities and p53 expression. Gen Diagn Pathol 1995;141:97–103.
  • Dobashi Y, Takei N, Suzuki S, Yoneyama H, Hanawa M, Ooi A. Aberration of epidermal growth factor receptor expression in bone and soft-tissue tumors: protein overexpression, gene amplification and activation of downstream molecules. Mod Pathol 2004;17:1497–1505.
  • Lee JA, Ko Y, Kim DH, Lim JS, Kong CB, Cho WH, Jeon DG, Lee SY, Koh JS. Epidermal growth factor receptor: is it a feasible target for the treatment of osteosarcoma? Cancer Res Treat 2012;44:202–209.
  • Kersting C, Gebert C, Agelopoulos K, Schmidt H, van Diest PJ, Juergens H, Winkelmann W, Kevric M, Gosheger G, Brandt B, Bielack S, Buerger H. Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome. Clin Cancer Res 2007;13:2998–3005.
  • Wen YH, Koeppen H, Garcia R, Chiriboga L, Tarlow BD, Peters BA, Eigenbrot C, Yee H, Steiner G, Greco MA. Epidermal growth factor receptor in osteosarcoma: expression and mutational analysis. Hum Pathol 2007;38:1184–1191.
  • Wu H, Muscato NE, Gonzalez A, Shyr Y. An EGFR and AKT signaling pathway was identified with mediation model in osteosarcomas clinical study. Biomark Insights 20072:469–476.
  • Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer 2004;4:335–348.
  • Freeman SS, Allen SW, Ganti R, Wu J, Ma J, Su X, Neale G, Dome JS, Daw NC, Khoury JD. Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors. Cancer 2008;113:1453–1461.
  • Do SI, Jung WW, Kim HS, Park YK. The expression of epidermal growth factor receptor and its downstream signaling molecules in osteosarcoma. Int J Oncol 2009;34:797–803.
  • Angelucci A. Targeting ERBB receptors to inhibit metastasis: old hopes and new certainties. Curr Cancer Drug Targets 2009;9:1–18.
  • Okamoto I, Kenyon LC, Emlet DR, Mori T, Sasaki J, Hirosako S, Ichikawa Y, Kishi H, Godwin AK, Yoshioka M, Suga M, Matsumoto M, Wong AJ. Expression of constitutively activated EGFRvIII in non-small cell lung cancer. Cancer Sci 2003;94:50–56.
  • Charpidou A, Blatza D, Anagnostou V, Syrigos KN. Review. EGFR mutations in non-small cell lung cancer—clinical implications. In Vivo 2008;22:529–536.
  • Montero AJ, Diaz-Montero CM, Mao L, Youssef EM, Estecio M, Shen L, Issa JP. Epigenetic inactivation of EGFR by CpG island hypermethylation in cancer. Cancer biology & therapy 2006;5:1494–1501.
  • Fellenberg J, Krauthoff A, Pollandt K, Delling G, Parsch D. Evaluation of the predictive value of Her-2/neu gene expression on osteosarcoma therapy in laser-microdissected paraffin-embedded tissue. Lab Invest 2004;84:113–121.
  • Maitra A, Wanzer D, Weinberg AG, Ashfaq R. Amplification of the HER-2/neu oncogene is uncommon in pediatric osteosarcomas. Cancer 2001;92:677–683.
  • Onda M, Matsuda S, Higaki S, ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 1996;77:71–78.
  • Gorlick R, Huvos AG, Heller G, Aledo A, Beardsley GP, Healey JH, Meyers PA. Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 1999;17:2781–2788.
  • Zhou H, Randall RL, Brothman AR, Maxwell T, Coffin CM, Goldsby RE. Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol 2003;25:27–32.
  • Scotlandi K, Manara MC, Hattinger CM, Benini S, Perdichizzi S, Pasello M, Bacci G, Zanella L, Bertoni F, Picci P, Serra M. Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing's sarcoma. Eur J Cancer. 2005;41:1349–1361.
  • Ahmed N, Salsman VS, Yvon E, Louis CU, Perlaky L, Wels WS, Dishop MK, Kleinerman EE, Pule M, Rooney CM, Heslop HE, Gottschalk S. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Mol Ther 2009;17:1779–1787.
  • Hughes DP, Thomas DG, Giordano TJ, McDonagh KT, Baker LH. Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition. Pediatr Blood Cancer 2006;46:614–623.
  • Kilpatrick SE, Geisinger KR, King TS, Sciarrotta J, Ward WG, Gold SH, Bos GD. Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. Mod Pathol 2001;14:1277–1283.
  • Anninga JK, van de Vijver MJ, Cleton-Jansen AM, Kristel PM, Taminiau AH, Nooij M, Egeler RM, Hogendoorn PC. Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas. Eur J Cancer. 2004;40:963–970.
  • Thomas DG, Giordano TJ, Sanders D, Biermann JS, Baker L. Absence of HER2/neu gene expression in osteosarcoma and skeletal Ewing's sarcoma. Clin Cancer Res 2002;8:788–793.
  • Hughes DP, Thomas DG, Giordano TJ, Baker LH, McDonagh KT. Cell surface expression of epidermal growth factor receptor and Her-2 with nuclear expression of Her-4 in primary osteosarcoma. Cancer Res 2004;64:2047–2053.
  • Willmore-Payne C, Holden JA, Zhou H, Gupta D, Hirschowitz S, Wittwer CT, Layfield LJ. Evaluation of Her-2/neu gene status in osteosarcoma by fluorescence in situ hybridization and multiplex and monoplex polymerase chain reactions. Arch Pathol Lab Med 2006;130:691–698.
  • Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, Turc-Carel C, Triche TJ. The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 1994;331: 294–299.
  • Kim GY, Park JH, Kim YW, Jung WW, Unni KK, Park YK. Absence of amplification of HER-2/neu (c-erbB-2) gene in Ewing's sarcoma: a real-time polymerase chain reaction method. Pathol Res Pract 2004;200:663–667.
  • Ye D, Maitra A, Timmons CF, Leavey PJ, Ashfaq R, Ilaria RL, Jr. The epidermal growth factor receptor HER2 is not a major therapeutic target in Ewing sarcoma. J Pediatr Hematol Oncol 2003;25:459–466.
  • Zhou Z, Jia SF, Hung MC, Kleinerman ES. E1A sensitizes HER2/neu-overexpressing Ewing's sarcoma cells to topoisomerase II-targeting anticancer drugs. Cancer Res 2001;61:3394–3398.
  • Kang HG, Jenabi JM, Zhang J, Keshelava N, Shimada H, May WA, Ng T, Reynolds CP, Triche TJ, Sorensen PH. E-cadherin cell-cell adhesion in Ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res 2007;67:3094–3105.
  • Mendoza-Naranjo A, El-Naggar A, Wai DH, Mistry P, Lazic N, Ayala FR, da Cunha IW, Rodriguez-Viciana P, Cheng H, Tavares Guerreiro Fregnani JH, Reynolds P, Arceci RJ, Nicholson A, Triche TJ, Soares FA, Flanagan AM, Wang YZ, Strauss SJ, Sorensen PH. ERBB4 confers metastatic capacity in Ewing sarcoma. EMBO Mol Med 2013;5:1019–1034.
  • Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol 2012;13:e69–e76.
  • Gagliardi F, Boari N, Riva P, Mortini P. Current therapeutic options and novel molecular markers in skull base chordomas. Neurosurg Rev 2012;35:1–13; discussion 13–14.
  • Ptaszynski K, Szumera-Cieckiewicz A, Owczarek J, Mrozkowiak A, Pekul M, Baranska J, Rutkowski P. Epidermal growth factor receptor (EGFR) status in chordoma. Pol J Pathol 2009;60:81–87.
  • Dewaele B, Maggiani F, Floris G, Ampe M, Vanspauwen V, Wozniak A, Debiec-Rychter M, Sciot R. Frequent activation of EGFR in advanced chordomas. Clin Sarcoma Res 2011;1:4.
  • Shalaby A, Presneau N, Ye H, Halai D, Berisha F, Idowu B, Leithner A, Liegl B, Briggs TR, Bacsi K, Kindblom LG, Athanasou N, Amary MF, Hogendoorn PC, Tirabosco R, Flanagan AM. The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic target. J Pathol 2011;223:336–346.
  • Tamborini E, Virdis E, Negri T, Orsenigo M, Brich S, Conca E, Gronchi A, Stacchiotti S, Manenti G, Casali PG, Pierotti MA, Pilotti S. Analysis of receptor tyrosine kinases (RTKs) and downstream pathways in chordomas. Neuro Oncol 2010;12:776–789.
  • Fasig JH, Dupont WD, LaFleur BJ, Olson SJ, Cates JM. Immunohistochemical analysis of receptor tyrosine kinase signal transduction activity in chordoma. Neuropathol Appl Neurobiol 2008;34:95–104.
  • de Castro CV, Guimaraes G, Aguiar S, Jr Lopes A, Baiocchi G, da Cunha IW, Campos AH, Soares FA, Begnami MD. Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome. Hum Pathol 2013;44:1747–1755.
  • Weinberger PM, Yu Z, Kowalski D, Joe J, Manger P, Psyrri A, Sasaki CT. Differential expression of epidermal growth factor receptor, c-Met, and HER2/neu in chordoma compared with 17 other malignancies. Arch Otolaryngol Head Neck Surg 2005;131:707–711.
  • Deniz ML, Kilic T, Almaata I, Kurtkaya O, Sav A, Pamir MN. Expression of growth factors and structural proteins in chordomas: basic fibroblast growth factor, transforming growth factor alpha, and fibronectin are correlated with recurrence. Neurosurgery 2002;51:753–760; discussion 760.
  • Hof H, Welzel T, Debus J. Effectiveness of Cetuximab/Gefitinib in the therapy of a sacral chordoma. Onkologie 2006;29:572–574.
  • Linden O, Stenberg L, Kjellen E. Regression of cervical spinal cord compression in a patient with chordoma following treatment with Cetuximab and Gefitinib. Acta Oncol 2009;48:158–159.
  • Singhal N, Kotasek D, Parnis FX. Response to Erlotinib in a patient with treatment refractory chordoma. Anticancer Drugs 2009;20:953–955.
  • Launay SG, Chetaille B, Medina F, Perrot D, Nazarian S, Guiramand J, Moureau-Zabotto L, Bertucci F. Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review. BMC Cancer 2011;11:423.
  • Weiss SW, Goldblum JR, Enzinger FM. Enzinger and Weiss's soft tissue tumors. Elsevier Health Sciences, 2001.
  • Gusterson B, Cowley G, McIlhinney J, Ozanne B, Fisher C, Reeves B. Evidence for increased epidermal growth factor receptors in human sarcomas. Int J Cancer 1985;36:689–693.
  • Barbashina V, Benevenia J, Aviv H, Tsai J, Patterson F, Aisner S, Cohen S, Fernandes H, Skurnick J, Hameed M. Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases. J Cancer Res Clin Oncol 2002;128:610–616.
  • Tawbi H, Thomas D, Lucas DR, Biermann JS, Schuetze SM, Hart AL, Chugh R, Baker LH. Epidermal growth factor receptor expression and mutational analysis in synovial sarcomas and malignant peripheral nerve sheath tumors. Oncologist 2008;13:459–466.
  • Bode B, Frigerio S, Behnke S, Senn B, Odermatt B, Zimmermann DR, Moch H. Mutations in the tyrosine kinase domain of the EGFR gene are rare in synovial sarcoma. Mod Pathol 2006;19:541–547.
  • Thomas DG, Giordano TJ, Sanders D, Biermann S, Sondak VK, Trent JC, Yu D, Pollock RE, Baker L. Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma. Cancer 2005;103:830–838.
  • Teng HW, Wang HW, Chen WM, Chao TC, Hsieh YY, Hsih CH, Tzeng CH, Chen PC, Yen CC. Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma. J Surg Oncol 2011;103:773–781.
  • Nuciforo PG, Pellegrini C, Fasani R, Maggioni M, Coggi G, Parafioriti A, Bosari S. Molecular and immunohistochemical analysis of HER2/neu oncogene in synovial sarcoma. Hum Pathol 2003;34:639–645.
  • Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998;338:153–160.
  • Crew AJ, Clark J, Fisher C, Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J 1995;14:2333–2340.
  • Allander SV, Illei PB, Chen Y, Antonescu CR, Bittner M, Ladanyi M, Meltzer PS. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol 2002;161:1587–1595.
  • Parham DM, Ellison DA. Rhabdomyosarcomas in adults and children: an update. Arch Pathol Lab Med 2006;130:1454–1465.
  • Xia SJ, Pressey JG, Barr FG. Molecular pathogenesis of rhabdomyosarcoma. Cancer Biol Ther 2002;1:97–104.
  • Punyko JA, Mertens AC, Gurney JG, Yasui Y, Donaldson SS, Rodeberg DA, Raney RB, Stovall M, Sklar CA, Robison LL, Baker KS. Long-term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study. Pediatr Blood Cancer 2005;44:643–653.
  • Ganti R, Skapek SX, Zhang J, Fuller CE, Wu J, Billups CA, Breitfeld PP, Dalton JD, Meyer WH, Khoury JD. Expression and genomic status of EGFR and ErbB-2 in alveolar and embryonal rhabdomyosarcoma. Mod Pathol 2006;19:1213–1220.
  • Nordberg J, Mpindi JP, Iljin K, Pulliainen AT, Kallajoki M, Kallioniemi O, Elenius K, Elenius V. Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar rhabdomyosarcoma. PLoS One 2012;7:e50819.
  • Ricci C, Landuzzi L, Rossi I, De Giovanni C, Nicoletti G, Astolfi A, Pupa S, Menard S, Scotlandi K, Nanni P, Lollini PL. Expression of HER/erbB family of receptor tyrosine kinases and induction of differentiation by glial growth factor 2 in human rhabdomyosarcoma cells. Int J Cancer 2000;87:29–36.
  • Andrechek ER, Hardy WR, Girgis-Gabardo AA, Perry RL, Butler R, Graham FL, Kahn RC, Rudnicki MA, Muller WJ. ErbB2 is required for muscle spindle and myoblast cell survival. Mol Cell Biol 2002;22:4714–4722.
  • De Giovanni C, Landuzzi L, Frabetti F, Nicoletti G, Griffoni C, Rossi I, Mazzotti M, Scotto L, Nanni P, Lollini PL. Antisense epidermal growth factor receptor transfection impairs the proliferative ability of human rhabdomyosarcoma cells. Cancer Res 1996;56:3898–3901.
  • Nanni P, Nicoletti G, De Giovanni C, Croci S, Astolfi A, Landuzzi L, Di Carlo E, Iezzi M, Musiani P, Lollini PL. Development of rhabdomyosarcoma in HER-2/neu transgenic p53 mutant mice. Cancer Res 2003;63:2728–2732.
  • Yewale C, Baradia D, Vhora I, Patil S, Misra A. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials 2013;34:8690–8707.
  • Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 2003;21:2787–2799.
  • Ebb D, Meyers P, Grier H, Bernstein M, Gorlick R, Lipshultz SE, Krailo M, Devidas M, Barkauskas DA, Siegal GP, Ferguson WS, Letson GD, Marcus K, Goorin A, Beardsley P, Marina N. Phase II trial of Trastuzumab in combination with cytotoxic chemotherapy for treatment of metastatic osteosarcoma with human epidermal growth factor receptor 2 overexpression: a report from the children's oncology group. J Clin Oncol 2012;30:2545–2551.
  • Pahl JH, Ruslan SE, Buddingh EP, Santos SJ, Szuhai K, Serra M, Gelderblom H, Hogendoorn PC, Egeler RM, Schilham MW, Lankester AC. Anti-EGFR antibody Cetuximab enhances the cytolytic activity of natural killer cells toward osteosarcoma. Clin Cancer Res 2012;18:432–441.
  • Imai K, Takaoka A. Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 2006;6:714–727.
  • Daw NC, Furman WL, Stewart CF, Iacono LC, Krailo M, Bernstein ML, Dancey JE, Speights RA, Blaney SM, Croop JM, Reaman GH, Adamson PC. Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol 2005;23:6172–6180.
  • Furman WL, Navid F, Daw NC, McCarville MB, McGregor LM, Spunt SL, Rodriguez-Galindo C, Panetta JC, Crews KR, Wu J, Gajjar AJ, Houghton PJ, Santana VM, Stewart CF. Tyrosine kinase inhibitor enhances the bioavailability of oral Irinotecan in pediatric patients with refractory solid tumors. J Clin Oncol 2009;27:4599–4604.
  • van Cruijsen H, Voest EE, Punt CJ, Hoekman K, Witteveen PO, Meijerink MR, Puchalski TA, Robertson J, Saunders O, Jurgensmeier JM, van Herpen CM, Giaccone G. Phase I evaluation of Cediranib, a selective VEGFR signalling inhibitor, in combination with Gefitinib in patients with advanced tumours. Eur J Cancer. 2010;46:901–911.
  • Jimeno A, Daw NC, Amador ML, Cusatis G, Kulesza P, Krailo M, Ingle AM, Blaney SM, Adamson P, Hidalgo M. Analysis of biologic surrogate markers from a Children's Oncology Group Phase I trial of Gefitinib in pediatric patients with solid tumors. Pediatr Blood Cancer 2007;49:352–357.
  • Ray-Coquard I, Le Cesne A, Whelan JS, Schoffski P, Bui BN, Verweij J, Marreaud S, van Glabbeke M, Hogendoorn P, Blay JY. A phase II study of Gefitinib for patients with advanced HER-1 expressing synovial sarcoma refractory to doxorubicin-containing regimens. Oncologist 2008;13:467–473.
  • Jakacki RI, Hamilton M, Gilbertson RJ, Blaney SM, Tersak J, Krailo MD, Ingle AM, Voss SD, Dancey JE, Adamson PC. Pediatric phase I and pharmacokinetic study of erlotinib followed by the combination of Erlotinib and Temozolomide: a Children's Oncology Group Phase I Consortium Study. J Clin Oncol 2008;26:4921–4927.
  • Long XH, Zhang GM, Peng AF, Luo QF, Zhang L, Wen HC, Zhou RP, Gao S, Zhou Y, Liu ZL. Lapatinib alters the malignant phenotype of osteosarcoma cells via downregulation of the activity of the HER2-PI3K/AKT-FASN axis in vitro. Oncol Rep 2014;31:328–334.
  • Stacchiotti S, Tamborini E, Lo Vullo S, Bozzi F, Messina A, Morosi C, Casale A, Crippa F, Conca E, Negri T, Palassini E, Marrari A, Palmerini E, Mariani L, Gronchi A, Pilotti S, Casali PG. Phase II study on Lapatinib in advanced EGFR-positive chordoma. Ann Oncol 2013;24:1931–1936.

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