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Extensive research has been concentrated on identifying and developing MMP inhibitors for cancer treatment, including melanoma, with particular focus on MMP\u20102, MMP\u20109 and MMP\u201014. MMP\u20102 and MMP\u20109 are gelatinases involved in collagen degradation, tumour invasion and angiogenesis, while MMP\u201014 activates other MMPs and promotes tumour cell migration. Early broad\u2010spectrum 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\u2010target effects seen with earlier broad\u2010spectrum 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\u2010inflammatory and immune\u2010modulatory 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\u2010to\u2010date overview of the advancements and therapeutic prospects of both synthetic and natural MMP inhibitors in melanoma treatment.<\/jats:p>","DOI":"10.1111\/exd.70203","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:46:43Z","timestamp":1768625203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Matrix Metalloproteinase Inhibition in Melanoma"],"prefix":"10.1111","volume":"35","author":[{"given":"Ellie","family":"Zhang","sequence":"first","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Thakur","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine 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