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Progress and challenge in development of biotherapeutics targeting MET receptor for treatment of advanced cancer

Hang-Ping Yao1, Rachel Hudson2, Ming-Hai Wang3

  • 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|September 22, 2020
PubMed

Insights

Targeting the MET receptor tyrosine kinase shows promise for treating advanced epithelial cancers like gastric and lung tumors. Antibody-based therapies offer a future direction for improving patient survival and achieving curative outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Advanced epithelial cancers (gastric, lung, pancreatic) exhibit invasive growth, metastasis, chemoresistance, and stemness.
  • Current therapies (antibodies, kinase inhibitors, checkpoint blockades) offer benefits but fall short of curative outcomes.
  • The MET receptor tyrosine kinase is crucial in epithelial cancer initiation, progression, and malignancy, with elevated expression correlating with poor prognosis.

Purpose of the Study:

  • To review the critical role of MET in epithelial tumorigenesis.
  • To discuss the development and clinical potential of antibody-based biotherapeutics targeting MET.
  • To highlight MET-targeted therapies as a future strategy for advanced epithelial cancers.

Main Methods:

  • Literature review of preclinical and clinical studies on MET and its targeted therapies.
  • Analysis of MET's function in cancer initiation, progression, and metastasis.
  • Evaluation of antibody-based biotherapeutics, including bispecific antibodies and antibody-drug conjugates.

Main Results:

  • MET is a key driver of epithelial cancer malignancy and progression.
  • Increased MET expression is a significant prognostic indicator for patient survival.
  • Antibody-based biotherapeutics targeting MET demonstrate therapeutic potential.

Conclusions:

  • MET is a validated therapeutic target for epithelial cancers.
  • Antibody-based biotherapeutics, including bispecific antibodies and ADCs, show promise for clinical application.
  • Targeting MET offers a future strategy to improve outcomes in advanced epithelial cancers.
Keywords:
Antibody-drug conjugatesBispecific antibodyClinical trialsEpithelial cancersMETMonoclonal antibodyPharmaceutical targetPharmacokineticsReceptor tyrosine kinaseTherapeutic efficacyToxicological activityTumorigenesis

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