# Targeting Pathways Implicated in Cholesterol Metabolism for Novel Cancer Therapy

## TL;DR

This review explores how cholesterol metabolism influences cancer growth and highlights key proteins that could be targeted for new cancer therapies.

## Contribution

The paper provides a comprehensive overview of cholesterol metabolism pathways and their role in cancer, identifying potential molecular targets for novel anticancer strategies.

## Key findings

- Dysregulated cholesterol metabolism contributes to tumorigenesis and cancer progression through pathways like SREBP, NPC1, PCSK9, and SOAT1.
- Targeting cholesterol-related proteins offers a promising direction for developing metabolism-based cancer therapies.
- Preclinical and clinical evidence suggests that high-fat diets may exacerbate cancer development through cholesterol signaling.

## Abstract

Cholesterol is known for its function in cell metabolism and lipid transport, but it also serves as a powerful signal that can influence cancer growth. This review seeks to understand the various pathways and mechanisms through which the dysregulation of cholesterol metabolism is implicated in cancer growth and signaling, focusing on key molecular target proteins involved in cholesterol synthesis, transport, and metabolism. Additionally, the review further assesses the potential for targeting these key pathways and proteins as a future strategy of anticancer treatment and therapy.

Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Research over the past decade has highlighted cholesterol metabolism as a key modulator of cancer development and a promising therapeutic target. By integrating mechanistic and translational evidence, this review seeks to clarify how cholesterol metabolism interfaces with oncogenic signaling and set directions for future investigation. Accumulating preclinical and clinical data suggest that dysregulated cholesterol levels, often associated with high-fat diets, may contribute to tumorigenesis and malignant transformation. Implicated pathways, such as SREBP, NPC1, PCSK9, and SOAT1, orchestrate various processes of lipid metabolism, including cholesterol synthesis, esterification, receptor degradation, and transport, that harbor a tumorigenic environment and promote oncogenic processes. Additionally, these enzymes and corresponding pathways provide a promising direction for developing metabolism-oriented anticancer strategies. Cholesterol metabolism dysregulation serves as a major avenue for cancer signaling and growth, but studies also highlight key molecular mechanisms and targets for future treatments. Future studies should focus on expanding studies into further cancer types, investigating combination therapies, and developing novel inhibitors of key molecular targets.