Top

Published in:

Open Access 01-12-2014 | Review

Targeting of erbB3 receptor to overcome resistance in cancer treatment

Authors: Jian Ma, Hui Lyu, Jingcao Huang, Bolin Liu

Published in: Molecular Cancer | Issue 1/2014

Abstract

The erbB receptors, including the epidermal growth factor receptor (EGFR), erbB2 (also known as HER2/neu), erbB3 (or HER3), and erbB4 (or HER4), are often aberrantly activated in a wide variety of human cancers. They are excellent targets for selective anti-cancer therapies because of their transmembrane location and pro-oncogenic activity. While several therapeutic agents against erbB2 and/or EGFR have been used in the treatment of human cancers with efficacy, there has been relatively less emphasis on erbB3 as a molecular target. Elevated expression of erbB3 is frequently observed in various malignancies, where it promotes tumor progression via interactions with other receptor tyrosine kinases (RTKs) due to its lack of or weak intrinsic kinase activity. Studies on the underlying mechanisms implicate erbB3 as a major cause of treatment failure in cancer therapy, mainly through activation of the PI-3 K/Akt, MEK/MAPK, and Jak/Stat signaling pathways as well as Src kinase. It is believed that inhibition of erbB3 signaling may be required to overcome therapeutic resistance and effectively treat cancers. To date, no erbB3-targeted therapy has been approved for cancer treatment. Targeting of erbB3 receptor with a monoclonal antibody (Ab) is the only strategy currently under preclinical study and clinical evaluation. In this review, we focus on the role of erbB3-initiated signaling in the development of cancer drug resistance and discuss the latest advances in identifying therapeutic strategies inactivating erbB3 to overcome the resistance and enhance efficacy of cancer therapeutics.

Available only for authorised users

Baselga J, Swain SM: Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009, 9: 463-475. 10.1038/nrc2656PubMed

Hynes NE, MacDonald G: ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009, 21: 177-184. 10.1016/j.ceb.2008.12.010PubMed

Olayioye MA, Neve RM, Lane HA, Hynes NE: The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000, 19: 3159-3167. 10.1093/emboj/19.13.3159PubMedCentralPubMed

Ferguson KM, Berger MB, Mendrola JM, Cho HS, Leahy DJ, Lemmon MA: EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell. 2003, 11: 507-517. 10.1016/S1097-2765(03)00047-9PubMed

Burgess AW, Cho H-S, Eigenbrot C, Ferguson KM, Garrett TP, Leahy DJ, Lemmon MA, Sliwkowski MX, Ward CW, Yokoyama S: An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell. 2003, 12: 541-552. 10.1016/S1097-2765(03)00350-2PubMed

Cho H-S, Leahy DJ: Structure of the extracellular region of HER3 reveals an interdomain tether. Sci Signal. 2002, 297: 1330-

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. 10.1200/JCO.2003.01.504PubMed

Ogiso H, Ishitani R, Nureki O, Fukai S, Yamanaka M, Kim J-H, Saito K, Sakamoto A, Inoue M, Shirouzu M: Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002, 110: 775-787. 10.1016/S0092-8674(02)00963-7PubMed

Boudeau J, Miranda-Saavedra D, Barton GJ, Alessi DR: Emerging roles of pseudokinases. Trends Cell Biol. 2006, 16: 443-452. 10.1016/j.tcb.2006.07.003PubMed

10.

Citri A, Skaria KB, Yarden Y: The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res. 2003, 284: 54-65. 10.1016/S0014-4827(02)00101-5PubMed

11.

Shi F, Telesco SE, Liu Y, Radhakrishnan R, Lemmon MA: ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc Natl Acad Sci U S A. 2010, 107: 7692-7697. 10.1073/pnas.1002753107PubMedCentralPubMed

12.

Schulze WX, Deng L, Mann M: Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol. 2005, 1: 2005.0008-PubMedCentralPubMed

13.

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. 1997, 16: 1647-1655. 10.1093/emboj/16.7.1647PubMedCentralPubMed

14.

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. 2010, 21: 944-950. 10.1016/j.semcdb.2010.08.007PubMedCentralPubMed

15.

Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF, Hynes NE: The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A. 2003, 100: 8933-8938. 10.1073/pnas.1537685100PubMedCentralPubMed

16.

Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, Sliwkowski MX, Stern HM: A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008, 68: 5878-5887. 10.1158/0008-5472.CAN-08-0380PubMed

17.

Jathal MK, Chen L, Mudryj M, Ghosh PM: Targeting ErbB3: the New RTK(id) on the Prostate Cancer Block. Immunol Endocr Metab Agents Med Chem. 2011, 11: 131-149. 10.2174/187152211795495643PubMedCentralPubMed

18.

Mills GB, Yarden Y: The rebirth of a phoenix: ovarian cancers are addicted to ErbB-3. Cancer Cell. 2010, 17: 217-218. 10.1016/j.ccr.2010.02.023PubMed

19.

Sheng Q, Liu X, Fleming E, Yuan K, Piao H, Chen J, Moustafa Z, Thomas RK, Greulich H, Schinzel A, Zaghlul S, Batt D, Ettenberg S, Meyerson M, Schoeberl B, Kung AL, Hahn WC, Drapkin R, Livingston DM, Liu JF: An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells. Cancer Cell. 2010, 17: 298-310.PubMedCentralPubMed

20.

Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Janne PA: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007, 316: 1039-1043. 10.1126/science.1141478PubMed

21.

Huang S, Li C, Armstrong EA, Peet CR, Saker J, Amler LC, Sliwkowski MX, Harari PM: Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation. Cancer Res. 2013, 73: 824-833. 10.1158/0008-5472.CAN-12-1611PubMed

22.

Schoeberl B, Faber AC, Li D, Liang MC, Crosby K, Onsum M, Burenkova O, Pace E, Walton Z, Nie L, Fulgham A, Song Y, Nielsen UB, Engelman JA, Wong KK: An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer Res. 2010, 70: 2485-2494. 10.1158/0008-5472.CAN-09-3145PubMedCentralPubMed

23.

Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, Linggi B, Kalra A, Paragas V, Bukhalid R, Grantcharova V, Kohli N, West KA, Leszczyniecka M, Feldhaus MJ, Kudla AJ, Nielsen UB: Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal. 2009, 2: ra31-PubMed

24.

Li C, Brand TM, Iida M, Huang S, Armstrong EA, van der Kogel A, Wheeler DL: Human epidermal growth factor receptor 3 (HER3) blockade with U3-1287/AMG888 enhances the efficacy of radiation therapy in lung and head and neck carcinoma. Discov Med. 2013, 16: 79-92.PubMedCentralPubMed

25.

McDonagh CF, Huhalov A, Harms BD, Adams S, Paragas V, Oyama S, Zhang B, Luus L, Overland R, Nguyen S, Gu J, Kohli N, Wallace M, Feldhaus MJ, Kudla AJ, Schoeberl B, Nielsen UB: Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol Cancer Ther. 2012, 11: 582-593. 10.1158/1535-7163.MCT-11-0820PubMed

26.

Berger MB, Mendrola JM, Lemmon MA: ErbB3/HER3 does not homodimerize upon neuregulin binding at the cell surface. FEBS Lett. 2004, 569: 332-336. 10.1016/j.febslet.2004.06.014PubMed

27.

Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, Di Fiore PP, Kraus MH: Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995, 10: 1813-1821.PubMed

28.

Hsieh AC, Moasser MM: Targeting HER proteins in cancer therapy and the role of the non-target HER3. Br J Cancer. 2007, 97: 453-457. 10.1038/sj.bjc.6603910PubMedCentralPubMed

29.

Wallasch C, Weiss FU, Niederfellner G, Jallal B, Issing W, Ullrich A: Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J. 1995, 14: 4267-4275.PubMedCentralPubMed

30.

Chakrabarty A, Rexer BN, Wang SE, Cook RS, Engelman JA, Arteaga CL: H1047R phosphatidylinositol 3-kinase mutant enhances HER2-mediated transformation by heregulin production and activation of HER3. Oncogene. 2010, 29: 5193-5203. 10.1038/onc.2010.257PubMedCentralPubMed

31.

Liu B, Ordonez-Ercan D, Fan Z, Edgerton SM, Yang X, Thor AD: Downregulation of erbB3 abrogates erbB2-mediated tamoxifen resistance in breast cancer cells. Int J Cancer. 2007, 120: 1874-1882. 10.1002/ijc.22423PubMed

32.

Liu B, Ordonez-Ercan D, Fan Z, Huang X, Edgerton SM, Yang X, Thor AD: Estrogenic promotion of ErbB2 tyrosine kinase activity in mammary tumor cells requires activation of ErbB3 signaling. Mol Cancer Res. 2009, 7: 1882-1892.PubMed

33.

Beji A, Horst D, Engel J, Kirchner T, Ullrich A: Toward the prognostic significance and therapeutic potential of HER3 receptor tyrosine kinase in human colon cancer. Clin Cancer Res. 2012, 18: 956-968. 10.1158/1078-0432.CCR-11-1186PubMed

34.

Maurer CA, Friess H, Kretschmann B, Zimmermann A, Stauffer A, Baer HU, Korc M, Buchler MW: Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2. Hum Pathol. 1998, 29: 771-777. 10.1016/S0046-8177(98)90444-0PubMed

35.

Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, Chaudhuri S, Pujara K, Guillory J, Edgar KA, Janakiraman V, Scholz RP, Bowman KK, Lorenzo M, Li H, Wu J, Yuan W, Peters BA, Kan Z, Stinson J, Mak M, Modrusan Z, Eigenbrot C, Firestein R, Stern HM, Rajalingam K, Schaefer G, Merchant MA, Sliwkowski MX, de Sauvage FJ: Oncogenic ERBB3 mutations in human cancers. Cancer Cell. 2013, 23: 603-617. 10.1016/j.ccr.2013.04.012PubMed

36.

Grupka NL, Lear-Kaul KC, Kleinschmidt-DeMasters BK, Singh M: Epidermal growth factor receptor status in breast cancer metastases to the central nervous system. Comparison with HER-2/neu status. Arch Pathol Lab Med. 2004, 128: 974-979.PubMed

37.

Bieche I, Onody P, Tozlu S, Driouch K, Vidaud M, Lidereau R: Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer. 2003, 106: 758-765. 10.1002/ijc.11273PubMed

38.

deFazio A, Chiew YE, Sini RL, Janes PW, Sutherland RL: Expression of c-erbB receptors, heregulin and oestrogen receptor in human breast cell lines. Int J Cancer. 2000, 87: 487-498. 10.1002/1097-0215(20000815)87:4<487::AID-IJC5>3.0.CO;2-JPubMed

39.

Kim A, Liu B, Ordonez-Ercan D, Alvarez KM, Jones LD, McKimmey C, Edgerton SM, Yang X, Thor AD: Functional interaction between mouse erbB3 and wild-type rat c-neu in transgenic mouse mammary tumor cells. Breast Cancer Res. 2005, 7: R708-718. 10.1186/bcr1281PubMedCentralPubMed

40.

Siegel PM, Ryan ED, Cardiff RD, Muller WJ: Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J. 1999, 18: 2149-2164. 10.1093/emboj/18.8.2149PubMedCentralPubMed

41.

Liles JS, Arnoletti JP, Tzeng C-WD, Howard JH, Kossenkov AV, Kulesza P, Heslin MJ, Frolov A: ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma. Cancer Biol Ther. 2010, 10: 555-563. 10.4161/cbt.10.6.12532PubMedCentralPubMed

42.

Reschke M, Mihic-Probst D, van der Horst EH, Knyazev P, Wild PJ, Hutterer M, Meyer S, Dummer R, Moch H, Ullrich A: HER3 is a determinant for poor prognosis in melanoma. Clin Cancer Res. 2008, 14: 5188-5197. 10.1158/1078-0432.CCR-08-0186PubMed

43.

Barnes NL, Khavari S, Boland GP, Cramer A, Knox WF, Bundred NJ: Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast. Clin Cancer Res. 2005, 11: 2163-2168. 10.1158/1078-0432.CCR-04-1633PubMed

44.

Naidu R, Yadav M, Nair S, Kutty MK: Expression of c-erbB3 protein in primary breast carcinomas. Br J Cancer. 1998, 78: 1385-1390. 10.1038/bjc.1998.689PubMedCentralPubMed

45.

Quinn CM, Ostrowski JL, Lane SA, Loney DP, Teasdale J, Benson FA: c-erbB-3 protein expression in human breast cancer: comparison with other tumour variables and survival. Histopathology. 1994, 25: 247-252. 10.1111/j.1365-2559.1994.tb01324.xPubMed

46.

Lemoine NR, Barnes DM, Hollywood DP, Hughes CM, Smith P, Dublin E, Prigent SA, Gullick WJ, Hurst HC: Expression of the ERBB3 gene product in breast cancer. Br J Cancer. 1992, 66: 1116-1121. 10.1038/bjc.1992.420PubMedCentralPubMed

47.

Travis A, Pinder SE, Robertson JF, Bell JA, Wencyk P, Gullick WJ, Nicholson RI, Poller DN, Blamey RW, Elston CW, Ellis IO: C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators. Br J Cancer. 1996, 74: 229-233. 10.1038/bjc.1996.342PubMedCentralPubMed

48.

Pawlowski V, Revillion F, Hebbar M, Hornez L, Peyrat JP: Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res. 2000, 6: 4217-4225.PubMed

49.

Sassen A, Rochon J, Wild P, Hartmann A, Hofstaedter F, Schwarz S, Brockhoff G: Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 2008, 10: R2- 10.1186/bcr1843PubMedCentralPubMed

50.

Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM: Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol. 2003, 200: 290-297. 10.1002/path.1370PubMed

51.

Koutras AK, Kalogeras KT, Dimopoulos MA, Wirtz RM, Dafni U, Briasoulis E, Pectasides D, Gogas H, Christodoulou C, Aravantinos G, Zografos G, Timotheadou E, Papakostas P, Linardou H, Razis E, Economopoulos T, Kalofonos HP, Fountzilas G: Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Br J Cancer. 2008, 99: 1775-1785. 10.1038/sj.bjc.6604769PubMedCentralPubMed

52.

Lee Y, Cho S, Seo JH, Shin BK, Kim HK, Kim I, Kim A: Correlated expression of erbB-3 with hormone receptor expression and favorable clinical outcome in invasive ductal carcinomas of the breast. Am J Clin Pathol. 2007, 128: 1041-1049. 10.1309/GA5VRFQFY5D0MVKDPubMed

53.

Lee H, Akita RW, Sliwkowski MX, Maihle NJ: A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulin-stimulated activation of ErbB2, ErbB3, and ErbB4. Cancer Res. 2001, 61: 4467-4473.PubMed

54.

Offterdinger M, Schofer C, Weipoltshammer K, Grunt TW: c-erbB-3: a nuclear protein in mammary epithelial cells. J Cell Biol. 2002, 157: 929-939. 10.1083/jcb.200109033PubMedCentralPubMed

55.

Chiu CG, Masoudi H, Leung S, Voduc DK, Gilks B, Huntsman DG, Wiseman SM: HER-3 overexpression is prognostic of reduced breast cancer survival: a study of 4046 patients. Ann Surg. 2010, 251: 1107-1116. 10.1097/SLA.0b013e3181dbb77ePubMed

56.

Ocana A, Vera-Badillo F, Seruga B, Templeton A, Pandiella A, Amir E: HER3 overexpression and survival in solid tumors: a meta-analysis. J Natl Cancer Inst. 2013, 105: 266-273. 10.1093/jnci/djs501PubMed

57.

Campbell MR, Amin D, Moasser MM: HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy. Clin Cancer Res. 2010, 16: 1373-1383. 10.1158/1078-0432.CCR-09-1218PubMedCentralPubMed

58.

Mattoon D, Lamothe B, Lax I, Schlessinger J: The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3 K/Akt cell survival pathway. BMC Biol. 2004, 2: 24- 10.1186/1741-7007-2-24PubMedCentralPubMed

59.

Suenaga A, Takada N, Hatakeyama M, Ichikawa M, Yu X, Tomii K, Okimoto N, Futatsugi N, Narumi T, Shirouzu M: Novel mechanism of interaction of p85 subunit of phosphatidylinositol 3-kinase and ErbB3 receptor-derived phosphotyrosyl peptides. J Biol Chem. 2005, 280: 1321-1326. 10.1074/jbc.M410436200PubMed

60.

Knuefermann C, Lu Y, Liu B, Jin W, Liang K, Wu L, Schmidt M, Mills GB, Mendelsohn J, Fan Z: HER2/PI-3 K/Akt activation leads to a multidrug resistance in human breast adenocarcinoma cells. Oncogene. 2003, 22: 3205-3212. 10.1038/sj.onc.1206394PubMed

61.

Newby JC, Johnston S, Smith IE, Dowsett M: Expression of epidermal growth factor receptor and c-erbB2 during the development of tamoxifen resistance in human breast cancer. Clin Cancer Res. 1997, 3: 1643-1651.PubMed

62.

Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, Schiff R: Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2–positive breast cancer. J Natl Cancer Inst. 2004, 96: 926-935. 10.1093/jnci/djh166PubMed

63.

Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK: Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat. 1992, 24: 85-95. 10.1007/BF01961241PubMed

64.

Pietras RJ, Arboleda J, Reese DM, Wongvipat N, Pegram MD, Ramos L, Gorman CM, Parker MG, Sliwkowski MX, Slamon DJ: HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene. 1995, 10: 2435-PubMed

65.

Tang CK, Perez C, Grunt T, Waibel C, Cho C, Lupu R: Involvement of heregulin-β2 in the acquisition of the hormone-independent phenotype of breast cancer cells. Cancer Res. 1996, 56: 3350-3358.PubMed

66.

Tovey S, Dunne B, Witton CJ, Forsyth A, Cooke TG, Bartlett JM: Can molecular markers predict when to implement treatment with aromatase inhibitors in invasive breast cancer?. Clin Cancer Res. 2005, 11: 4835-4842. 10.1158/1078-0432.CCR-05-0196PubMed

67.

Seruga B, Tannock IF: Chemotherapy-based treatment for castration-resistant prostate cancer. J Clin Oncol. 2011, 29: 3686-3694. 10.1200/JCO.2010.34.3996PubMed

68.

Kruser TJ, Wheeler DL: Mechanisms of resistance to HER family targeting antibodies. Exp Cell Res. 2010, 316: 1083-1100. 10.1016/j.yexcr.2010.01.009PubMed

69.

Vlacich G, Coffey RJ: Resistance to EGFR-targeted therapy: a family affair. Cancer Cell. 2011, 20: 423-425. 10.1016/j.ccr.2011.10.006PubMedCentralPubMed

70.

Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, Ercan D, Rogers A, Roncalli M, Takeda M, Fujisaka Y, Philips J, Shimizu T, Maenishi O, Cho Y, Sun J, Destro A, Taira K, Takeda K, Okabe T, Swanson J, Itoh H, Takada M, Lifshits E, Okuno K, Engelman JA, Shivdasani RA, Nishio K, Fukuoka M, Varella-Garcia M: Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011, 3: 99ra86-PubMedCentralPubMed

71.

Abel EV, Basile KJ, Kugel CH, Witkiewicz AK, Le K, Amaravadi RK, Karakousis GC, Xu X, Xu W, Schuchter LM, Lee JB, Ertel A, Fortina P, Aplin AE: Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J Clin Invest. 2013, 123: 2155-2168. 10.1172/JCI65780PubMedCentralPubMed

72.

Montero-Conde C, Ruiz-Llorente S, Dominguez JM, Knauf JA, Viale A, Sherman EJ, Ryder M, Ghossein RA, Rosen N, Fagin JA: Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas. Cancer Discov. 2013, 3: 520-533. 10.1158/2159-8290.CD-12-0531PubMedCentralPubMed

73.

Sartor AO: Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space. J Hematol Oncol. 2011, 4: 18- 10.1186/1756-8722-4-18PubMedCentralPubMed

74.

Bezler M, Hengstler JG, Ullrich A: Inhibition of doxorubicin-induced HER3-PI3K-AKT signalling enhances apoptosis of ovarian cancer cells. Mol Oncol. 2012, 6: 516-529. 10.1016/j.molonc.2012.07.001PubMed

75.

Huang X, Gao L, Wang S, McManaman JL, Thor AD, Yang X, Esteva FJ, Liu B: Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-i receptor in breast cancer cells resistant to herceptin. Cancer Res. 2010, 70: 1204-1214. 10.1158/0008-5472.CAN-09-3321PubMed

76.

Wang S, Huang X, Lee CK, Liu B: Elevated expression of erbB3 confers paclitaxel resistance in erbB2-overexpressing breast cancer cells via upregulation of Survivin. Oncogene. 2010, 29: 4225-4236. 10.1038/onc.2010.180PubMed

77.

Clark AS, West K, Streicher S, Dennis PA: Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther. 2002, 1: 707-717.PubMed

78.

Friedrichs WE, Russell DH, Donzis EJ, Middleton AK, Silva JM, Roth RA, Hidalgo M: Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity. Clin Cancer Res. 2004, 10: 8059-8067. 10.1158/1078-0432.CCR-04-0035PubMed

79.

Jordan NJ, Gee JM, Barrow D, Wakeling AE, Nicholson RI: Increased constitutive activity of PKB/Akt in tamoxifen resistant breast cancer MCF-7 cells. Breast Cancer Res Treat. 2004, 87: 167-180. 10.1023/B:BREA.0000041623.21338.47PubMed

80.

Agus DB, Akita RW, Fox WD, Lewis GD, Higgins B, Pisacane PI, Lofgren JA, Tindell C, Evans DP, Maiese K, Scher HI, Sliwkowski MX: Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell. 2002, 2: 127-137. 10.1016/S1535-6108(02)00097-1PubMed

81.

Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M: Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). [comment]. J Natl Cancer Inst. 2001, 93: 1852-1857. 10.1093/jnci/93.24.1852PubMed

82.

Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ: Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005, 65: 11118-11128. 10.1158/0008-5472.CAN-04-3841PubMed

83.

Church DN, Talbot DC: Survivin in solid tumors: rationale for development of inhibitors. Curr Oncol Rep. 2012, 14: 120-128. 10.1007/s11912-012-0215-2PubMed

84.

Kanwar JR, Kamalapuram SK, Kanwar RK: Targeting survivin in cancer: the cell-signalling perspective. Drug Discov Today. 2011, 16: 485-494. 10.1016/j.drudis.2011.04.001PubMed

85.

Kelly RJ, Lopez-Chavez A, Citrin D, Janik JE, Morris JC: Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. Mol Cancer. 2011, 10: 35- 10.1186/1476-4598-10-35PubMedCentralPubMed

86.

Jiang N, Saba NF, Chen ZG: Advances in Targeting HER3 as an Anticancer Therapy. Chemother Res Pract. 2012, 2012: 817304-PubMedCentralPubMed

87.

Aurisicchio L, Marra E, Luberto L, Carlomosti F, De Vitis C, Noto A, Gunes Z, Roscilli G, Mesiti G, Mancini R, Alimandi M, Ciliberto G: Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors. J Cell Physiol. 2012, 227: 3381-3388. 10.1002/jcp.24037PubMed

88.

Aurisicchio L, Marra E, Roscilli G, Mancini R, Ciliberto G: The promise of anti-ErbB3 monoclonals as new cancer therapeutics. Oncotarget. 2012, 3: 744-758.PubMedCentralPubMed

89.

Foreman PK, Gore M, Kobel PA, Xu L, Yee H, Hannum C, Ho H, Wang SM, Tran HV, Horowitz M, Horowitz L, Bhatt RR: ErbB3 inhibitory surrobodies inhibit tumor cell proliferation in vitro and in vivo. Mol Cancer Ther. 2012, 11: 1411-1420. 10.1158/1535-7163.MCT-12-0068PubMed

90.

Wang S, Huang J, Lyu H, Cai B, Yang X, Li F, Tan J, Edgerton SM, Thor AD, Lee CK, Liu B: Therapeutic targeting of erbB3 with MM-121/SAR256212 enhances antitumor activity of paclitaxel against erbB2-overexpressing breast cancer. Breast Cancer Res. 2013, 15: R101- 10.1186/bcr3563PubMedCentralPubMed

91.

Huang J, Wang S, Lyu H, Cai B, Yang X, Wang J, Liu B: The anti-erbB3 antibody MM-121/SAR256212 in combination with trastuzumab exerts potent antitumor activity against trastuzumab-resistant breast cancer cells. Mol Cancer. 2013, 12: 134- 10.1186/1476-4598-12-134PubMedCentralPubMed

92.

Arnett SO, Teillaud J-L, Wurch T, Reichert JM, Dunlop DC, Huber M: IBC’s 21st Annual Antibody Engineering and 8th Annual Antibody Therapeutics International Conferences and 2010 Annual Meeting of The Antibody Society December 5–9, 2010. 2011, 133-152. San Diego, CA USA: MAbs. Landes Bioscience,

93.

Sala G, Traini S, D'Egidio M, Vianale G, Rossi C, Piccolo E, Lattanzio R, Piantelli M, Tinari N, Natali PG, Muraro R, Iacobelli S: An ErbB-3 antibody, MP-RM-1, inhibits tumor growth by blocking ligand-dependent and independent activation of ErbB-3/Akt signaling. Oncogene. 2012, 31: 1275-1286. 10.1038/onc.2011.322PubMed

94.

Sala G, Rapposelli IG, Ghasemi R, Piccolo E, Traini S, Capone E, Rossi C, Pelliccia A, Di Risio A, D'Egidio M, Tinari N, Muraro R, Iacobelli S: EV20, a Novel Anti-ErbB-3 Humanized Antibody, Promotes ErbB-3 Down-Regulation and Inhibits Tumor Growth In Vivo. Transl Oncol. 2013, 6: 676-684. 10.1593/tlo.13475PubMedCentralPubMed

95.

Wu Y, Zhang Y, Wang M, Li Q, Qu Z, Shi V, Kraft P, Kim S, Gao Y, Pak J, Youngster S, Horak ID, Greenberger LM: Downregulation of HER3 by a novel antisense oligonucleotide, EZN-3920, improves the antitumor activity of EGFR and HER2 tyrosine kinase inhibitors in animal models. Mol Cancer Ther. 2013, 12: 427-437. 10.1158/1535-7163.MCT-12-0838PubMed

96.

Huang X, Gao L, Wang S, Lee CK, Ordentlich P, Liu B: HDAC inhibitor SNDX-275 induces apoptosis in erbB2-overexpressing breast cancer cells via down-regulation of erbB3 expression. Cancer Res. 2009, 69: 8403-8411. 10.1158/0008-5472.CAN-09-2146PubMed

97.

Wang S, Huang J, Lyu H, Lee CK, Tan J, Wang J, Liu B: Functional cooperation of miR-125a, miR-125b, and miR-205 in entinostat-induced downregulation of erbB2/erbB3 and apoptosis in breast cancer cells. Cell Death Dis. 2013, 4: e556- 10.1038/cddis.2013.79PubMedCentralPubMed

98.

Wahdan-Alaswad R, Liu B: “Sister” miRNAs in cancers. Cell Cycle. 2013, 12: 3703-3704. 10.4161/cc.26875PubMedCentralPubMed

99.

Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD: Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 2001, 17: 615-675. 10.1146/annurev.cellbio.17.1.615PubMed

100.

Reddy KB, Nabha SM, Atanaskova N: Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 2003, 22: 395-403. 10.1023/A:1023781114568PubMed

101.

Summy JM, Gallick GE: Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 2003, 22: 337-358. 10.1023/A:1023772912750PubMed

102.

Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT, Horwitz AF: FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol. 2004, 6: 154-161. 10.1038/ncb1094PubMed

103.

Xue C, Liang F, Mahmood R, Vuolo M, Wyckoff J, Qian H, Tsai K-L, Kim M, Locker J, Zhang Z-Y, Segall JE: ErbB3-Dependent Motility and Intravasation in Breast Cancer Metastasis. Cancer Res. 2006, 66: 1418-1426. 10.1158/0008-5472.CAN-05-0550PubMed

Title: Targeting of erbB3 receptor to overcome resistance in cancer treatment
Authors: Jian Ma
Hui Lyu
Jingcao Huang
Bolin Liu
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-13-105

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

MicroRNA-26b suppresses the NF-κB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3

TCAB1: a potential target for diagnosis and therapy of head and neck carcinomas

Profilin-1 suppresses tumorigenicity in pancreatic cancer through regulation of the SIRT3-HIF1α axis

Induction of integrin α2 in a highly bone metastatic human prostate cancer cell line: roles of RANKL and AR under three-dimensional suspension culture

miR-2909-mediated regulation of KLF4: a novel molecular mechanism for differentiating between B-cell and T-cell pediatric acute lymphoblastic leukemias

SNAI1 is critical for the aggressiveness of prostate cancer cells with low E-cadherin

Keynote webinar | Spotlight on antibody–drug conjugates in cancer