Development of Antibody-based C-Met Inhibitors for Targeted Cancer Therapy

Overview

Journal Immunotargets Ther

Publisher Dove Medical Press

Specialty Allergy & Immunology

Date 2016 Jul 30

PMID 27471710

Citations 15

Authors

Dongheon Lee

Eun-Sil Sung

Jin-Hyung Ahn

Sungwon An

Jiwon Huh

Weon-Kyoo You

Affiliations

Soon will be listed here.

Abstract

Signaling pathways mediated by receptor tyrosine kinases (RTKs) and their ligands play important roles in the development and progression of human cancers, which makes RTK-mediated signaling pathways promising therapeutic targets in the treatment of cancer. Compared with small-molecule compounds, antibody-based therapeutics can more specifically recognize and bind to ligands and RTKs. Several antibody inhibitors of RTK-mediated signaling pathways, such as human epidermal growth factor receptor 2, vascular endothelial growth factor, epidermal growth factor receptor or vascular endothelial growth factor receptor 2, have been developed and are widely used to treat cancer patients. However, since the therapeutic options are still limited in terms of therapeutic efficacy and types of cancers that can be treated, efforts are being made to identify and evaluate novel RTK-mediated signaling pathways as targets for more efficacious cancer treatment. The hepatocyte growth factor/c-Met signaling pathway has come into the spotlight as a promising target for development of potent cancer therapeutic agents. Multiple antibody-based therapeutics targeting hepatocyte growth factor or c-Met are currently in preclinical or clinical development. This review focuses on the development of inhibitors of the hepatocyte growth factor/c-Met signaling pathway for cancer treatment, including critical issues in clinical development and future perspectives for antibody-based therapeutics.

Citing Articles

The therapeutic potential of RNA m(6)A in lung cancer.

Yu J, Sun W, Zhao X, Chen Y Cell Commun Signal. 2024; 22(1):617.

PMID: 39736743 PMC: 11687105. DOI: 10.1186/s12964-024-01980-5.

c-MET and the immunological landscape of cancer: novel therapeutic strategies for enhanced anti-tumor immunity.

Jabbarzadeh Kaboli P, Roozitalab G, Farghadani R, Eskandarian Z, Zerrouqi A Front Immunol. 2024; 15():1498391.

PMID: 39664377 PMC: 11632105. DOI: 10.3389/fimmu.2024.1498391.

Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies.

Iweala E, Amuji D, Oluwajembola A, Ugbogu E Curr Res Pharmacol Drug Discov. 2024; 7:100204.

PMID: 39524211 PMC: 11543557. DOI: 10.1016/j.crphar.2024.100204.

Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies.

Hussein Mer A, Mirzaei Y, Misamogooe F, Bagheri N, Bazyari A, Keshtkaran Z Drug Deliv Transl Res. 2024; 14(11):2963-2988.

PMID: 38597995 DOI: 10.1007/s13346-024-01564-3.

Recent progress in the imaging of c-Met aberrant cancers with positron emission tomography.

Floresta G, Abbate V Med Res Rev. 2022; 42(4):1588-1606.

PMID: 35292998 PMC: 9314990. DOI: 10.1002/med.21885.

References

Mizuno S, Matsumoto K, Li M, Nakamura T . HGF reduces advancing lung fibrosis in mice: a potential role for MMP-dependent myofibroblast apoptosis. FASEB J. 2005; 19(6):580-2. DOI: 10.1096/fj.04-1535fje. View

Giusti R, Shastri K, Cohen M, Keegan P, Pazdur R . FDA drug approval summary: panitumumab (Vectibix). Oncologist. 2007; 12(5):577-83. DOI: 10.1634/theoncologist.12-5-577. View

Garrett C, Eng C . Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther. 2011; 11(7):937-49. DOI: 10.1517/14712598.2011.582464. View

Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A . Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989; 342(6248):440-3. DOI: 10.1038/342440a0. View

Uehara Y, Minowa O, Mori C, Shiota K, KUNO J, Noda T . Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature. 1995; 373(6516):702-5. DOI: 10.1038/373702a0. View

Xu A, Huang P . Receptor tyrosine kinase coactivation networks in cancer. Cancer Res. 2010; 70(10):3857-60. PMC: 2875162. DOI: 10.1158/0008-5472.CAN-10-0163. View

Iveson T, Donehower R, Davidenko I, Tjulandin S, Deptala A, Harrison M . Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014; 15(9):1007-18. DOI: 10.1016/S1470-2045(14)70023-3. View

Roy S, Narang B, Rastogi S, Rawal R . A novel multiple tyrosine-kinase targeted agent to explore the future perspectives of anti-angiogenic therapy for the treatment of multiple solid tumors: cabozantinib. Anticancer Agents Med Chem. 2014; 15(1):37-47. DOI: 10.2174/1871520614666140902153840. View

Goyal L, Muzumdar M, Zhu A . Targeting the HGF/c-MET pathway in hepatocellular carcinoma. Clin Cancer Res. 2013; 19(9):2310-8. PMC: 4583193. DOI: 10.1158/1078-0432.CCR-12-2791. View

10.

Osada S, Matsui S, Komori S, Yamada J, Sanada Y, Ihawa A . Effect of hepatocyte growth factor on progression of liver metastasis in colorectal cancer. Hepatogastroenterology. 2010; 57(97):76-80. View

11.

Que W, Chen J, Chuang M, Jiang D . Knockdown of c-Met enhances sensitivity to bortezomib in human multiple myeloma U266 cells via inhibiting Akt/mTOR activity. APMIS. 2012; 120(3):195-203. DOI: 10.1111/j.1600-0463.2011.02836.x. View

12.

Sulpice E, Ding S, Muscatelli-Groux B, Berge M, Han Z, Plouet J . Cross-talk between the VEGF-A and HGF signalling pathways in endothelial cells. Biol Cell. 2009; 101(9):525-39. DOI: 10.1042/BC20080221. View

13.

Okamoto W, Okamoto I, Tanaka K, Hatashita E, Yamada Y, Kuwata K . TAK-701, a humanized monoclonal antibody to hepatocyte growth factor, reverses gefitinib resistance induced by tumor-derived HGF in non-small cell lung cancer with an EGFR mutation. Mol Cancer Ther. 2010; 9(10):2785-92. PMC: 3208321. DOI: 10.1158/1535-7163.MCT-10-0481. View

14.

Scagliotti G, Novello S, von Pawel J . The emerging role of MET/HGF inhibitors in oncology. Cancer Treat Rev. 2013; 39(7):793-801. DOI: 10.1016/j.ctrv.2013.02.001. View

15.

Huh C, Factor V, Sanchez A, Uchida K, Conner E, Thorgeirsson S . Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A. 2004; 101(13):4477-82. PMC: 384772. DOI: 10.1073/pnas.0306068101. View

16.

Poole R, Vaidya A . Ramucirumab: first global approval. Drugs. 2014; 74(9):1047-58. DOI: 10.1007/s40265-014-0244-2. View

17.

Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S . A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell. 1994; 77(2):261-71. DOI: 10.1016/0092-8674(94)90318-2. View

18.

Cohen M, Shen Y, Keegan P, Pazdur R . FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009; 14(11):1131-8. DOI: 10.1634/theoncologist.2009-0121. View

19.

Lengyel E, Prechtel D, Resau J, Gauger K, Welk A, Lindemann K . C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. Int J Cancer. 2004; 113(4):678-82. DOI: 10.1002/ijc.20598. View

20.

Que W, Chen J . Knockdown of c-Met inhibits cell proliferation and invasion and increases chemosensitivity to doxorubicin in human multiple myeloma U266 cells in vitro. Mol Med Rep. 2011; 4(2):343-9. DOI: 10.3892/mmr.2011.426. View