Elucidating the role of medicinal plants in melanoma treatment: a review on metastatic progression and phytochemical intervention

Abstract

Metastatic melanoma remains one of the most highly aggressive and treatment-resistant cancers, highlighting the need for enhanced understanding of its progression and novel therapeutic strategies. The metastatic cascade is an intricate, dynamic, and coordinated series of events which initiates with melanoma cell proliferation and the release of regulatory signalling molecules, followed by angiogenesis in response to hypoxia and nutrient deprivation, and extracellular matrix (ECM) degradation and invasion via matrix metalloproteinase (MMP) activity. Intravasation generates circulating tumour cells (CTCs), which evade immune surveillance through platelet shielding before extravasating at distant sites to establish secondary tumours. Conventional metastatic melanoma treatments, including surgery, chemotherapy, radiotherapy, targeted inhibitors and immunotherapy, are associated with significant limitations, which has shifted the focus to the use of interventions obtained from natural product resources. In light of this, this narrative review aims to emphasise the potential of plant-derived candidates with anti-melanoma activity, including medicinal plant extracts and isolated phytochemicals, by bridging the gap between traditional medicine and modern oncology and permitting medicinal plants to serve as a compelling avenue for future melanoma management. Owing to the substantial heterogeneity in experimental models, extraction methods, phytochemical composition, and outcome measures, a quantitative comparison was deemed inappropriate, and the evidence was synthesised narratively. It was determined that several medicinal plants and their constituent phytochemicals demonstrate considerable promise as multitargeted therapeutic candidates against metastatic melanoma. However, the predominance of early-stage preclinical studies focused primarily on proliferation, limited investigation of the later stages of metastasis, insufficiently explored and documented long-term in vivo toxicological effects, and the absence of melanoma-specific clinical trials are major limitations to their clinical translation. To translate this potential into evidence-based melanoma treatments, future research should prioritise comprehensive antimetastatic, toxicological, and clinical investigations, and address key considerations such as the multi-target activity of plant extracts, standardisation, the importance of model selection, assumptions on botanical safety, bioavailability, and regulatory compliance.