# Matrix Metalloproteinase Inhibition in Melanoma

## TL;DR

This paper reviews the role of matrix metalloproteinase (MMP) inhibitors in treating melanoma, focusing on their potential to improve therapy by targeting specific MMPs and reducing side effects.

## Contribution

The paper provides an updated review of both synthetic and natural MMP inhibitors, emphasizing their therapeutic potential in melanoma treatment.

## Key findings

- Selective MMP inhibitors may improve treatment efficacy and reduce off-target effects compared to broad-spectrum inhibitors.
- Natural MMP inhibitors offer biocompatibility and additional benefits like antioxidant and anti-inflammatory properties.
- Recent studies suggest a shift toward targeted and combinatory treatment strategies for melanoma using MMP inhibitors.

## Abstract

Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix (ECM) and are found to participate in all stages of tumour progression including modifying signalling pathways, regulating cytokines and promoting tumour growth, particularly by inducing angiogenesis and facilitating cancer spread. Extensive research has been concentrated on identifying and developing MMP inhibitors for cancer treatment, including melanoma, with particular focus on MMP‐2, MMP‐9 and MMP‐14. MMP‐2 and MMP‐9 are gelatinases involved in collagen degradation, tumour invasion and angiogenesis, while MMP‐14 activates other MMPs and promotes tumour cell migration. Early broad‐spectrum MMP inhibitors showed limited success and significant side effects. However, selective MMP inhibitors offer a more targeted approach that may address these problems. By focusing on specific MMPs essential for melanoma invasion, metastasis and angiogenesis, these inhibitors have the potential to improve treatment efficacy and reduce the off‐target effects seen with earlier broad‐spectrum therapies. Recent years have seen a marked increase in studies on natural MMP inhibitors for melanoma, driven by their biocompatibility and reduced side effects. In addition to inhibiting MMPs, many of these inhibitors also provide antioxidant, anti‐inflammatory and immune‐modulatory benefits, thus enhancing their therapeutic potential and overall effectiveness in cancer treatment. These findings highlight the promising role of MMP inhibitors in melanoma therapy, suggesting a shift towards more targeted and combinatory treatment strategies. This review aims to provide an up‐to‐date overview of the advancements and therapeutic prospects of both synthetic and natural MMP inhibitors in melanoma treatment.