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Published on: May 18, 2018
Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials
Yuriy P Mayasin1, Maria N Osinnikova1, Chulpan B Kharisova1
1Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Abstract:
Melanoma is a malignant, highly metastatic neoplasm showing increasing morbidity and mortality. Tumor invasion and angiogenesis are based on remodeling of the extracellular matrix (ECM). Selective inhibition of functional components of cell-ECM interaction, such as hyaluronic acid (HA), matrix metalloproteinases (MMPs), and integrins, may inhibit tumor progression and enhance the efficacy of combination treatment with immune checkpoint inhibitors (ICIs), chemotherapy, or immunotherapy. In this review, we combine the results of different approaches targeting extracellular matrix elements in melanoma in preclinical and clinical studies. The identified limitations of many approaches, including side effects, low selectivity, and toxicity, indicate the need for further studies to optimize therapy. Nevertheless, significant progress in expanding our understanding of tumor biology and the development of targeted therapies holds great promise for the early approaches developed several decades ago to inhibit metastasis through ECM targeting.
Insights
Targeting extracellular matrix (ECM) components like hyaluronic acid (HA) and matrix metalloproteinases (MMPs) shows promise for inhibiting melanoma metastasis. Further research is needed to overcome limitations and optimize these ECM-targeting therapies.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Melanoma is a dangerous cancer known for spreading rapidly.
- Tumor growth and spread depend on changes in the extracellular matrix (ECM).
- Key ECM components include hyaluronic acid (HA), matrix metalloproteinases (MMPs), and integrins.
Purpose of the Study:
- To review current preclinical and clinical studies on targeting ECM elements in melanoma.
- To assess the potential of inhibiting cell-ECM interactions to control melanoma progression.
- To evaluate combination therapies involving ECM targeting and other cancer treatments.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of therapeutic strategies targeting ECM components in melanoma.
- Evaluation of combination treatments with immune checkpoint inhibitors (ICIs), chemotherapy, and immunotherapy.
Main Results:
- Targeting ECM components like HA, MMPs, and integrins can inhibit melanoma invasion and angiogenesis.
- Combination therapies may enhance treatment efficacy.
- Limitations such as side effects, low selectivity, and toxicity were identified.
Conclusions:
- Targeting the ECM offers a promising strategy for melanoma treatment.
- Further research is required to optimize therapies and overcome existing limitations.
- Understanding tumor biology and developing targeted therapies are crucial for improving melanoma outcomes.
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