Targeting the c-MET signaling pathway for cancer therapy

被引:47
作者
Liu, Xiangdong [1 ]
Yao, Wenqing [1 ]
Newton, Robert C. [1 ]
Scherle, Peggy A. [1 ]
机构
[1] Incyte Corp, Expt Stn, Wilmington, DE 19880 USA
关键词
cancer; c-MET; hepatocyte growth factor; receptor tyrosine kinase; signal transduction; small-molecule kinase inhibitor;
D O I
10.1517/13543784.17.7.997
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: In many human cancers, c-MET is activated via receptor overexpression, amplification, mutation and/or a ligand-dependent autocrine/ paracrine loop. These biochemical and genetic abnormalities have been correlated with poor clinical outcomes and drug resistance in cancer patients. Preclinical studies suggest that targeting aberrant c-MET signaling could be an attractive therapy in cancer, but this notion has only recently been tested in the clinic. Objectives: To describe the biological aspects. of the c-MET signaling pathway and to discuss recent progress and possible future trends in the. development of agents that target the c-MET pathway, with an emphasis on small-molecule c-MET kinase inhibitors. Method: A review of relevant publications, including published articles in literature, reports at scientific meetings, and information available through the Internet. Results/conclusion: The dysregulated c-MET pathway represents a promising target for cancer, drug development. The agents that target the c-MET pathway have demonstrated impressive evidence of early clinical activity and may have a significant therapeutic potential.
引用
收藏
页码:997 / 1011
页数:15
相关论文
共 141 条
  • [1] Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis
    Abounader, R
    Laterra, J
    [J]. NEURO-ONCOLOGY, 2005, 7 (04) : 436 - 451
  • [2] Akervall J, 2004, CLIN CANCER RES, V10, P8204, DOI 10.1158/1078-0432.CCR-04-0722
  • [3] Met receptor signaling: A key effector in esophageal adenocarcinoma
    Anderson, Mark R.
    Harrison, Rebecca
    Atherfold, Paul A.
    Campbell, Moray J.
    Darnton, S. Jane
    Obszynska, Jolanta
    Jankowski, Janusz A. Z.
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (20) : 5936 - 5943
  • [4] *ASCO, 2007, BUILD MOM PFIZ ONC F
  • [5] Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance
    Ayhan, A
    Ertunc, D
    Tok, EC
    Ayhan, A
    [J]. INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2005, 15 (04) : 618 - 623
  • [6] Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells
    Bauer, Todd W.
    Somcio, Ray J.
    Fan, Fan
    Liu, Wenbiao
    Johnson, Marjorie
    Lesslie, Donald P.
    Evans, Douglas B.
    Gallick, Gary E.
    Ellis, Lee M.
    [J]. MOLECULAR CANCER THERAPEUTICS, 2006, 5 (07) : 1676 - 1682
  • [7] Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas
    Baykal, C
    Ayhan, A
    Al, A
    Yüce, K
    Ayhan, A
    [J]. GYNECOLOGIC ONCOLOGY, 2003, 88 (02) : 123 - 129
  • [8] MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
    Bean, James
    Brennan, Cameron
    Shih, Jin-Yuan
    Riely, Gregory
    Viale, Agnes
    Wang, Lu
    Chitale, Dhananjay
    Motoi, Noriko
    Szoke, Janos
    Broderick, Stephen
    Balak, Marissa
    Chang, Wen-Cheng
    Yu, Chong-Jen
    Gazdar, Adi
    Pass, Harvey
    Rusch, Valerie
    Gerald, William
    Huang, Shiu-Feng
    Yang, Pan-Chyr
    Miller, Vincent
    Ladany, Marc
    Yang, Chih-Hsin
    Pao, William
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (52) : 20932 - 20937
  • [9] Met, metastasis, motility and more
    Birchmeier, C
    Birchmeier, W
    Gherardi, E
    Vande Woude, GF
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (12) : 915 - 925
  • [10] ESSENTIAL ROLE FOR THE C-MET RECEPTOR IN THE MIGRATION OF MYOGENIC PRECURSOR CELLS INTO THE LIMB BUD
    BLADT, F
    RIETHMACHER, D
    ISENMANN, S
    AGUZZI, A
    BIRCHMEIER, C
    [J]. NATURE, 1995, 376 (6543) : 768 - 771