# Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer

## TL;DR

Breast cancer cells change how they use nutrients, creating metabolic vulnerabilities that could be targeted for new and more effective treatments.

## Contribution

This paper reviews key metabolic pathways in breast cancer and highlights their roles in tumor progression and potential as therapeutic targets.

## Key findings

- Metabolic reprogramming in breast cancer supports tumor growth and therapy resistance.
- Inhibiting metabolic pathways like glycolysis and glutaminolysis shows promise in preclinical models.
- Metabolic plasticity and tumor heterogeneity pose challenges for targeted therapies.

## Abstract

Breast cancer cells change the way they use nutrients to grow and survive, which makes their metabolism an important area for new treatments. These cells often rely on specific pathways, such as those that process sugar, amino acids, and fats, to produce energy and build essential components. Recent research shows that blocking these pathways can slow cancer growth and make existing treatments more effective. However, better understanding of these metabolic changes and their roles in different breast cancer subtypes could lead to more personalized therapies and improve outcomes for patients in the future.

Metabolic reprogramming is a defining feature of breast cancer, enabling tumor cells to sustain rapid proliferation, survive under stress, and resist therapy. Key pathways including glycolysis, glutaminolysis, lipid metabolism, and one-carbon metabolism, play central roles in meeting the energetic and biosynthetic demands of malignant cells. Enhanced glycolytic flux supports ATP generation and lactate production, while glutamine metabolism fuels the tricarboxylic acid cycle and provides nitrogen for nucleotide synthesis. Lipid metabolic pathways, particularly fatty acid synthesis, contribute to membrane biogenesis and signaling, and one-carbon metabolism driven by serine and glycine supplies methyl groups for epigenetic regulation and nucleotide production. These metabolic adaptations not only promote tumor growth but also create vulnerabilities that can be exploited therapeutically. Inhibiting these pathways has shown promise in preclinical models; however, challenges such as metabolic plasticity, tumor heterogeneity, and potential toxicity in normal tissues underscore the need for biomarker-driven strategies and rational combination therapies. Herein, we describe current knowledge of the role of these pathways in breast cancer progression, highlighting the role of key enzymes in promoting breast cancer tumor cell growth and in breast cancer prognoses.