Perspective of Targeting Cancer-Associated Fibroblasts in Melanoma

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment

Background:

• Melanoma remains an aggressive, treatment-resistant cancer despite advances in immunotherapy and targeted therapy.
• Current treatments for advanced or recurrent melanoma face challenges including limited response rates, severe side effects, and poor prognosis.
• The tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), plays a critical role in melanoma progression and drug resistance.

Purpose of the Study:

• To review the origin, activation, and heterogeneity of CAFs in melanoma.
• To examine the contribution of stromal fibroblasts to melanoma development and metastasis.
• To highlight recent advancements in targeting CAFs and tumor-stroma interactions for melanoma treatment.

Main Methods:

• Literature review of preclinical studies and clinical applications.
• Analysis of the reprogramming mechanisms of local fibroblasts.
• Examination of CAF contributions at different melanoma developmental stages.

Main Results:

• CAFs remodel the extracellular matrix and secrete factors that promote melanoma growth, angiogenesis, inflammation, and metastasis.
• Stromal fibroblasts have been shown to promote melanoma cell proliferation.
• Targeting CAFs can create a tumor-resistant environment, potentially inhibiting melanoma growth across different genetic mutations.

Conclusions:

• Combination therapy co-targeting tumor cells and CAFs may improve therapeutic outcomes and overcome resistance.
• Further research into CAF origins and precise mechanisms is needed.
• Targeting CAFs represents a promising strategy for more effective melanoma treatment.