# Galectin-1 Inhibition as a Strategy for Malignant Peripheral Nerve Sheath Tumor Treatment

## TL;DR

This paper investigates using Galectin-1 inhibition with a compound called LLS30 to treat aggressive nerve tumors linked to neurofibromatosis.

## Contribution

A novel compound, LLS30, is developed to target the Galectin-1/Ras interaction, showing anti-tumor effects in MPNST models.

## Key findings

- LLS30 disrupts Galectin-1/Ras interaction, leading to Ras delocalization and reduced signaling.
- In vitro and in vivo experiments show LLS30 inhibits MPNST cell proliferation and tumor growth.
- Transcriptome analysis reveals downregulation of KRAS signaling and EMT-related pathways.

## Abstract

Neurofibromatosis type 1 (NF1) is an inherited disorder that predisposes individuals to malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive sarcoma with limited treatment options and poor prognosis. This study explores the potential of targeting the interaction between Galectin-1 and Ras as a novel therapeutic strategy for MPNSTs. Through molecular docking, we identified critical residues involved in the Galectin-1 and H-Ras interaction. We developed LLS30, a compound designed to target this Ras-binding pocket on Galectin-1, and tested its efficacy. LLS30 effectively disrupted the Galectin-1/Ras interaction, causing Ras delocalization from the plasma membrane and inhibiting Ras signaling. In vitro experiments showed that LLS30 significantly decreased MPNST cell proliferation and induced apoptosis. In vivo, LLS30 demonstrated potent anti-tumor effects, reducing tumor size, inhibiting metastasis, and extending survival in animal models. Transcriptome analysis further revealed the downregulation of KRAS signaling and inhibition of pathways associated with epithelial–mesenchymal transition. These findings suggest that targeting Galectin-1 with LLS30 offers therapeutic potential for MPNSTs and could be beneficial for other cancers driven by Galectin-1 and Ras signaling.