Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models

International Journal of Cancer

Volumn 130, Issue 10, 2012, Pages 2445-2454

  Cha, Mi Young ^a,b   Lee, Kwang Ok ^a   Kim, Mira ^a   Song, Ji Yeon ^a   Lee, Kyu Hang ^a   Park, Jongmin ^b   Chae, Yun Jung ^a   Kim, Young Hoon ^a   Suh, Kwee Hyun ^a   Lee, Gwan Sun ^a   Park, Seung Bum ^b   Kim, Maeng Sup ^a  

^a Hanmi Pharmaceutical Co Ltd   (South Korea)

^b Seoul National University   (South Korea)

Author keywords

breast cancer; EGFR T790M; erlotinib resistance; gastric cancer; HM781 36B; NSCLC; pan HER inhibitor

Indexed keywords

AFATINIB; CELL PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; HM 781 36B; LAPATINIB; PROTEIN HER4; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER RESISTANCE; CANCER SIZE; CONTROLLED STUDY; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; ENZYME INHIBITION; FEMALE; GENE MUTATION; HUMAN; HUMAN CELL; IC 50; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; OVARY CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; STOMACH CANCER; TREATMENT DURATION; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; HUMANS; LUNG NEOPLASMS; MICE; MICE, NUDE; PEPTIDE FRAGMENTS; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84859100127     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.26276     Document Type: Article

References (48)

1. Schlessinger J,. Cell signaling by receptor tyrosine kinases. Cell 2000; 103: 211-25.
2. Hynes NE, Lane HA,. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005; 5: 341-54. (Pubitemid 40637826)
3. Yarden Y, Sliwkowski MX,. Untangling the ErbB signaling network. Nat Rev Mol Cell Biol 2001; 2: 127-37.
4. Tang X, Shigematsu H, Bekele BN, Roth JA, Minna JD, Hong WK, Gazdar AF, Wistuba II,. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res 2005; 65: 7568-72. (Pubitemid 41297226)
5. Herbst RS, Langer CJ,. Epidermal growth factor receptors as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Semin Oncol 2002; 29: 27-36. (Pubitemid 34226516)
6. Traxler P, Bold G, Buchdunger E, Caravatti G, Furet P, Manley P, O'Reilly T, Wood J, Zimmermann J,. Tyrosine kinase inhibitors: from rational design to clinical trials. Med Res Rev 2001; 21: 499-512. (Pubitemid 32959239)
7. Adjei AA,. Epidermal growth factor receptor tyrosine kinase inhibitors in cancer therapy. Drugs Future 2001; 26: 1087-92. (Pubitemid 34059457)
8. Renhowe PA,. Inhibitors of growth factor receptor kinase-dependent signaling pathways in anticancer chemotherapy-clinical progress. Curr Opin Drug Discov Dev 2002; 5: 214-24. (Pubitemid 35012708)
9. Ranson M, Hammond LA, Ferry D, Kris M, Tullo A, Murray PI, Miller V, Averbuch S, Ochs J, Morris C, Feyereislova A, Swaisland H, et al. ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002; 20: 2240-50. (Pubitemid 34441651)
10. Ciardiello F, Tortora G,. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2001; 7: 2958-70. (Pubitemid 32963812)
11. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-57.
12. Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009; 361: 958-67.
13. Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ,. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 2007; 11: 217-27. (Pubitemid 46349842)
14. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008; 359: 366-77.
15. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H,. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005; 2: 1-11.
16. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B,. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352: 786-92. (Pubitemid 40271173)
17. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ,. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 2008; 105: 2070-5. (Pubitemid 351439466)
18. Balius TE, Rizzo RC,. Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry 2009; 48: 8435-48.
19. Sos ML, Rode HB, Heynck S, Peifer M, Fischer F, Klüter S, Pawar VG, Reuter C, Heuckmann JM, Weiss J, Ruddigkeit L, Rabiller M, et al. Chemogenomic profiling provides insights into the limited activity of irreversible EGFR inhibitors in tumor cells expressing the T790M EGFR resistance mutation. Cancer Res 2010; 70: 868-74.
20. Xia W, Mullin RJ, Keith BR, Liu LH, Ma H, Rusnak DW, Owens G, Alligood KJ, Spector NL,. Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 2002; 21: 6255-63.
21. Tanizaki J, Okamoto I, Takezawa K, Tsukioka S, Uchida J, Kiniwa M, Fukuoka M, Nakagawa K,. Synergistic antitumor effect of S-1 and HER2-targeting agents in gastric cancer with HER2 amplification. Mol Cancer Ther 2010; 9: 1198-207.
22. Johnston SR, Leary A,. Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today 2006; 42: 441-53. (Pubitemid 44221014)
23. Tsou HR, Overbeek-Klumpers EG, Hallett WA, Reich MF, Floyd MB, Johnson BD, Michalak RS, Nilakantan R, Discafani C, Golas J, Rabindran SK, Shen R, et al. Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity. J Med Chem 2005; 48: 1107-31. (Pubitemid 40270454)
24. Rabindran SK, Discafani CM, Rosfjord EC, Baxter M, Floyd MB, Golas J, Hallett WA, Johnson BD, Nilakantan R, Overbeek E, Reich MF, Shen R, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res 2004; 64: 3958-65. (Pubitemid 38697310)
25. Wissner A, Overbeek E, Reich MF, Floyd MB, Johnson BD, Mamuya N, Rosfjord EC, Discafani C, Davis R, Shi X, Rabindran SK, Gruber BC, et al. Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3- carbonitriles: the design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER-2). J Med Chem 2003; 46: 49-63. (Pubitemid 36043786)
26. Smaill JB, Showalter HD, Zhou H, Bridges AJ, McNamara DJ, Fry DW, Nelson JM, Sherwood V, Vincent PW, Roberts BJ, Elliott WL, Denny WA,. Tyrosine kinase inhibitors. 18. 6-Substituted 4-anilinoquinazolines and 4-anilinopyrido[3,4-d] pyrimidines as soluble, irreversible inhibitors of the epidermal growth factor receptor. J Med Chem 2001; 44: 429-40. (Pubitemid 32113588)
27. Campos S, Hamid O, Seiden MV, Oza A, Plante M, Potkul RK, Lenehan PF, Kaldjian EP, Varterasian ML, Jordan C, Charbonneau C, Hirte H,. Multicenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer. J Clin Oncol 2005; 23: 5597-604.
28. Engelman JA, Zejnullahu K, Gale CM, Lifshits E, Gonzales AJ, Shimamura T, Zhao F, Vincent PW, Naumov GN, Bradner JE, Althaus IW, Gandhi L, 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.
29. Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008; 27: 4702-11.
30. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497-500. (Pubitemid 38720929)
31. Kobayashi S, Ji H, Yuza Y, Meyerson M, Wong KK, Tenen DG, Halmos B,. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res 2005; 65: 7096-101. (Pubitemid 41161238)
32. Kwak EL, Sordella R, Bell DW, Godin-Heymann N, Okimoto RA, Brannigan BW, Harris PL, Driscoll DR, Fidias P, Lynch TJ, Rabindran SK, McGinnis JP, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci USA 2005; 102: 7665-70. (Pubitemid 40741028)
33. Nam HJ, Kim HP, Yoon YK, Hur HS, Song SH, Kim MS, Lee GS, Han SW, Im SA, Kim TY, Oh DY, Bang YJ,. Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer. Cancer Lett 2011; 302: 155-65.
34. Lee K-O, Cha MY, Kim M, Jung YH, Lee CG, Kim SY, Bang K, Park BW, Choi BI, Chae YJ, Ko MY, Kim HK, et al.; Hanmi Pharm. Co. Ltd., Novel amide derivative for inhibiting the growth of cancer cells. PCT patent WO 150,118, 2008.
35. Schnur SC, Arnold LD,; Pfizer Inc. Quinazoline derivatives. PCT patent WO 9,630,347, 1996.
36. Carter MC, Cockerill GS, Guntrip SB, Lackey KE, Smith KJ,; Glaxo Group Limited. Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors. PCT patent WO 9,935,146, 1999.
37. Himmelsbach F, Langkopf E, Blech S, Jung B, Baum E, Solca F,; Boehringer Ingelheim Pharma KG. Quinazoline derivatives, medicaments containing said compounds, their utilization and method for the production thereof. PCT patent WO 00,250,043, 2002.
38. Cha MY, Lee KO, Kim JW, Lee CG, Song JY, Kim YH, Lee GS, Park SB, Kim MS,. Discovery of a novel Her-1/Her-2 dual tyrosine kinase inhibitor for the treatment of Her-1 selective inhibitor-resistant non-small cell lung cancer. J Med Chem 2009; 52: 6880-8.
39. Hur W, Velentza A, Kim S, Flatauer L, Jiang X, Valente D, Mason DE, Suzuki M, Larson B, Zhang J, Zagorska A, Didonato M, et al. Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase. Bioorg Med Chem Lett 2008; 18: 5916-19.
40. Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, et al. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature 2009; 462: 1070-4.
41. Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H, Wistuba II, Fong KM, Toyooka S, Shimizu N, Fujisawa T, Minna JD, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005; 65: 1642-6. (Pubitemid 40478587)
42. Lewis GD, Figari I, Fendly B, Wong WL, Carter P, Gorman C, Shepard HM,. Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother 1993; 37: 255-63. (Pubitemid 23300507)
43. Naumov GN, Nilsson MB, Cascone T, Briggs A, Straume O, Akslen LA, Lifshits E, Byers LA, Xu L, Wu HK, Jänne P, Kobayashi S, et al. Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance. Clin Cancer Res 2009; 15: 3484-94.
44. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, Untch M, Rusnak DW, Spehar G, Mullin RJ, Keith BR, Gilmer TM, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006; 66: 1630-9. (Pubitemid 43259947)
45. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF,. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707-12. (Pubitemid 19147683)
46. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL,. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-82. (Pubitemid 17231334)
47. Eskens FA, Mom CH, Planting AS, Gietema JA, Amelsberg A, Huisman H, van Doorn L, Burger H, Stopfer P, Verweij J, de Vries EG,. A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 2008; 98: 80-5.
48. Stopfer P, Schaefer HG, Amelsberg A, Huisman H, Eskens FA, Gietema JA, Briscoe J, Lewis N, Cohen RB, Marshall J, Verweij J,. Pharmacokinetic results from two phase I dose escalation studies of once daily oral treatment with BIBW2992, an irreversible dual EGFR/HER2 receptor tyrosine kinase inhibitor, in patients with advanced solid tumors. In: AACR-NCI-EORTC International Conference on "Molecular Targets and Cancer Therapeutics", Philadelphia, PA, USA, November, 2005, no. B172.