# Acylcarnitines in Cancer Metabolism: Mechanistic Insights and Stratification Potential

## TL;DR

This paper reviews how acylcarnitines, molecules involved in fatty acid transport, play a role in cancer metabolism and could be used for early diagnosis and new therapies.

## Contribution

The paper provides mechanistic insights into acylcarnitines' role in cancer metabolism and their potential as biomarkers and therapeutic targets.

## Key findings

- Acylcarnitines leak into the bloodstream and can serve as non-invasive cancer biomarkers.
- Blocking acylcarnitine transport systems can sensitize cancer cells to chemotherapy.
- Altered acylcarnitine profiles reflect metabolic dynamics and can aid in cancer risk stratification.

## Abstract

Cancer cells rewire their metabolism to fuel rapid growth and survival. Recently, their dependence on fatty acids as a critical energy source has been recognized as a key survival strategy. This review explores the role of “acylcarnitines”, which are essential molecules acting as shuttles to transport fatty acids into mitochondria for energy production. We explain how cancer cells utilize this transport system to withstand metabolic stress and how specific acylcarnitines leak into the bloodstream. These leaked molecules can serve as non-invasive biomarkers, allowing for cancer detection through blood profiling. Furthermore, we discuss how blocking this transport system can starve cancer cells and overcome resistance to chemotherapy. This overview highlights acylcarnitines as promising targets for both early diagnosis and novel metabolic therapies.

Metabolic reprogramming constitutes a fundamental hallmark of malignancy, enabling cancer cells to sustain proliferation and survival under physiological stress. While aerobic glycolysis is well characterized, fatty acid oxidation (FAO) has emerged as a decisive driver of oncogenic progression and therapeutic resistance. Acylcarnitines (ACs), obligatory intermediates for the mitochondrial transport of long-chain fatty acids, have transcended their traditional categorization as passive metabolic byproducts to function as potent signaling entities and functional readouts of mitochondrial oxidative throughput. This review delineates the AC metabolic axis in oncology, examining the coordinated biochemical machinery, including the carnitine palmitoyltransferase (CPT) system, carnitine–acylcarnitine translocase (CACT; SLC25A20), and organic cation/carnitine transporter 2 (OCTN2), that governs cellular AC homeostasis. We further evaluate the clinical utility of altered AC profiles as non-invasive biomarkers for early diagnosis and risk stratification across diverse malignancies, highlighting their capacity to reflect metabolic bottlenecks and flux dynamics. Additionally, we scrutinize therapeutic strategies targeting the AC-FAO axis, demonstrating how the inhibition of key transporters and enzymes sensitizes tumors to conventional chemotherapy and immunotherapy. Ultimately, deciphering the systemic and spatial dynamics of ACs remains essential for advancing precision metabolic oncology and developing personalized therapeutic strategies based on metabolic profiling.