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Matrix Metalloproteinases in Chemoresistance: Regulatory Roles, Molecular Interactions, and Potential Inhibitors

Bernadette Xin Jie Tune1, Maw Shin Sim1, Chit Laa Poh2

  • 1Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur 50603, Malaysia.

Journal of Oncology
|May 19, 2022
PubMed

Insights

Matrix metalloproteinases (MMPs) drive cancer metastasis and chemoresistance by inducing epithelial-to-mesenchymal transition (EMT). Inhibiting MMPs offers a promising strategy to overcome treatment resistance in malignant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer metastasis and chemoresistance are leading causes of cancer mortality.
  • Epithelial-to-mesenchymal transition (EMT) is a shared pathway in metastasis and chemoresistance.
  • Matrix metalloproteinases (MMPs) are implicated in promoting cancer cell migration and metastasis via EMT.

Purpose of the Study:

  • To review the regulatory roles of specific MMPs in chemoresistance, focusing on EMT initiation and apoptosis resistance.
  • To discuss the diagnostic and prognostic potential of MMPs in cancer.
  • To explore strategies for MMP inhibition, including existing inhibitors and novel approaches like nanomaterials and epigenetic regulation.

Main Methods:

  • Literature review of studies on MMPs, EMT, chemoresistance, and cancer metastasis.
  • Analysis of molecular mechanisms linking MMPs to EMT and apoptosis resistance.
  • Evaluation of current and potential therapeutic strategies targeting MMPs.

Main Results:

  • MMPs play a critical role in inducing EMT, thereby facilitating cancer metastasis and chemoresistance.
  • Specific MMPs are associated with resistance to apoptosis, a key factor in treatment failure.
  • MMPs show potential as diagnostic and prognostic biomarkers for cancer.
  • Various strategies, including direct inhibition and upstream regulation, are being investigated to target MMPs for cancer therapy.

Conclusions:

  • Targeting MMPs represents a promising therapeutic avenue for overcoming chemoresistance in metastatic cancers.
  • Further research is needed to translate MMP-targeting strategies from preclinical studies to clinical application.
  • Understanding MMPs' role in EMT and apoptosis resistance is crucial for developing effective cancer treatments.

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