# Role of Galectin-1 in the Pathogenesis of Melanoma

## TL;DR

This paper reviews how Galectin-1 contributes to melanoma development and treatment resistance, and explores potential therapies targeting it.

## Contribution

A comprehensive review of Galectin-1's role in melanoma biology and therapeutic targeting, highlighting key research gaps.

## Key findings

- Galectin-1 influences immune evasion, metastasis, and therapy resistance in melanoma.
- Therapeutic strategies targeting Gal-1 include small-molecule inhibitors and imaging techniques.
- Gal-1's diverse roles in other systems limit its targeted therapies, requiring further research.

## Abstract

Galectins (Gal) are β-galactoside–binding endogenous lectins involved in a wide variety of angiogenic and immune functions throughout many tissues. Galectin 1 (Gal-1) is an important member of the galectin family, acting as a central regulator in immune cells, tumor immune evasion, metastasis, angiogenesis, and therapy resistance, especially in melanoma. Within the immune system, galectin-1 influences the activation of dendritic cells, natural killer cells, B-cells, and T-cells and their downstream effects, as well as influences myeloid-derived suppressor cells and tumor-associated macrophages. Further, Gal-1 influences cancer biology by promoting and regulating angiogenesis through the VEGFR2/NRP1 glycan binding signaling pathway and regulation of alternative splicing, and metastasis, priming pre-metastatic niches. Within melanoma, Gal-1 has a key role in therapy resistance, resisting MAPK inhibitors and chemotherapy, and cancer progression, including promoting immune evasion, SOX10-linked plasticity, and VEGF-independent angiogenesis. Therapeutic strategies have been developed to target the role of Galectin-1, including small-molecule and mAb Gal-1 inhibitors and positron emission tomography imaging for noninvasive profiling of tumor microenvironment. Despite its therapeutic potential, its vast role within different organ systems, including providing cardioprotective effects, immune system regulation, stress regulation, and axonal growth and regeneration, limits Gal-1 targeted therapies. Thus, further research is warranted to determine strategies to isolate therapeutic agents within the cancer cells. As Galectin-1 plays a role in the prognosis and treatment of melanoma, we critically reviewed the published information on its role within immune, endothelial, and stromal cells, the influence of Gal-1 on cancer biology, specifically within melanoma, therapeutic strategies to target Gal-1, and identified key gaps in current therapies and research.