Malondialdehyde and Oxidative Stress in Cancer - Biological Insights and Clinical Perspectives

Sep 22, 2026

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Malondialdehyde (MDA) is a principal end-product of lipid peroxidation and a widely used marker of oxidative stress and oxidative tissue damage. Beyond serving as a byproduct of polyunsaturated fatty acid peroxidation, MDA forms adducts with proteins and nucleic acids, supporting mutagenic, genotoxic, and cytotoxic mechanisms in carcinogenesis. This narrative review compiles evidence across multiple cancers and highlights associations with impaired antioxidant defenses, tumor burden, disease stage, and clinical outcomes. It also notes MDA’s non-specificity due to age, smoking, diet, metabolic disorders, inflammation, comorbidities, treatment exposure, and analytical methods.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Abstract

Keywords

1. Introduction

1.1. Oxidative Stress

Review Malondialdehyde and Oxidative Stress in Cancer: Biological Insights and Clinical Perspectives Federica Li Pomi 1,†, Maria Clara Gama de Souza Silva 2,†, Giuseppe Murdaca 3,4, *, Francesco Borgia 5, Adele Bottaro 6, Sebastiano Gangemi 2 and Alessandro Allegra 6 Academic Editor: Willibald Wonisch Received: 29 June 2026 Revised: 25 July 2026 Accepted: 27 July 2026 Published: 28 July 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy; [federicalipomi@hotmail.it](federicalipomi@hotmail.it) 2 Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; [claragamasouza@gmail.com](claragamasouza@gmail.com) (M.C.G.d.S.S.); [sebastiano.gangemi@unime.it](sebastiano.gangemi@unime.it) (S.G.) 3 Department of Internal Medicine, University of Genova, 16132 Genova, Italy 4 Allergology and Clinical Immunology Unit, San Bartolomeo Hospital, 19038 Sarzana, Italy 5 Section of Dermatology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; [fborgia@unime.it](fborgia@unime.it) 6 Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy; [bottarp15@gmail.com](bottarp15@gmail.com) (A.B.); [alessandro.allegra@unime.it](alessandro.allegra@unime.it) (A.A.) * Correspondence: [giuseppe.murdaca@unige.it](giuseppe.murdaca@unige.it)[ ](giuseppe.murdaca@unige.it)† These authors contributed equally to this work. Abstract Malondialdehyde (MDA) is one of the main end-products of lipid peroxidation (LPO) and represents a widely investigated marker of oxidative stress (OS) and oxidative tissue damage. Beyond its role as a measurable byproduct of polyunsaturated fatty acid peroxidation, MDA can interact with proteins and nucleic acids, generating adducts that may contribute to mutagenic, genotoxic, and cytotoxic events involved in carcinogenesis and tumor progression. This narrative review summarizes current evidence on the role of MDAin cancers, including breast, lung, head and neck, colorectal, cervical, and cutaneous tumors. Across these cancer types, increased circulating or tissue MDA levels have frequently been associated with enhanced LPO, impaired antioxidant defenses, tumor burden, advanced disease stage, aggressive histopathological features, treatment-related oxidative injury, and, in selected studies, poorer clinical outcomes. MDA-derived DNA adducts may further reflect oxidative DNA damage and provide mechanistic insight into the relationship between chronic redox imbalance, inflammation, and malignant transformation. However, MDA remains a non-specific biomarker influenced by age, smoking, diet, metabolic disorders, systemic inflammation, comorbidities, treatment exposure, and analytical methodology. Current evidence therefore supports MDA as a biologically relevant indicator of oxidative damage rather than a validated stand-alone diagnostic, prognostic, or therapeutic biomarker. Larger prospective studies using standardized and specific analytical methods are needed to clarify its clinical utility and to integrate MDA within broader redox biomarker panels. Keywords: malondialdehyde; lipid peroxidation; oxidative stress; cancer; skin cancer; colorectal cancer; lung cancer; cervical cancer 1. Introduction Reactive oxygen species (ROS) play a dual and context-dependent role in cancer biology. At controlled concentrations, they act as physiological signaling mediators, whereas persistent ROS accumulation may promote oxidative molecular damage, oncogenic signaling, and tumor progression. Conversely, when ROS levels exc

FAQs

What is malondialdehyde (MDA) and why is it important in oxidative stress research?

MDA is an end-product of lipid peroxidation and reflects oxidative stress and oxidative tissue damage. It is investigated as a marker because it can also form adducts with proteins and nucleic acids.

How can MDA contribute to cancer development and progression?

MDA can generate adducts that may lead to mutagenic, genotoxic, and cytotoxic events. These processes are linked to carcinogenesis and tumor progression, including oxidative DNA damage signals.

Why is MDA not considered a fully validated clinical biomarker on its own?

MDA is influenced by age, smoking, diet, metabolic disorders, systemic inflammation, comorbidities, treatment exposure, and analytical methodology, making it non-specific and limiting stand-alone diagnostic, prognostic, or therapeutic use.

Sep 22, 2026

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