Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities

Sep 23, 2026

Uploaded by McQueen

Breast cancer (BC) is a leading cause of cancer morbidity and mortality in women, with rising incidence worldwide and marked molecular heterogeneity across subtypes such as HER2-positive and triple-negative BC. Tumor aerobic glycolysis generates high lactate, which drives lactylation and alters tumor cell behavior alongside epigenetic and metabolic reprogramming. This review synthesizes current evidence on lactate metabolism and lactylation in BC, highlighting mechanistic insights and therapeutic strategies aimed at improving precision treatment, outcomes, and patient quality of life.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

Breast cancer heterogeneity and treatment challenges

Metabolic reprogramming and lactate in the tumor microenvironment

Lactylation in cancer biology

Lactylation as a post-translational modification

Cancer Biol Med 2025. doi: 10.20892/j.issn.2095-3941.2025.0173 REVIEW Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities Lan Huang1,2*, Xuemei Chen3*, Meina Yan1,2, Ze Xiang4, Jian Wu1,2* 1 Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215104, China; 2Suzhou Key Laboratory of Intelligent Critical Illness Biomarkers Translational Research, Suzhou 215104, China; 3Jiangsu Province Engineering Research Center of Development and Translation of Key Technologies for Chronic Disease Prevention and Control, Suzhou Vocational Health College, Suzhou 215009, China; 4Zhejiang University School of Medicine, Hangzhou 310009, China | ABSTRACT | Breast cancer (BC) has the highest prevalence among cancers specific to women, and its incidence rates are increasing in many countries. Subtypes of BC, including HER2-positive or triple-negative BC, exhibit differing treatment responses; consequently, demand for personalized therapy is increasing, and relevant precision medicine strategies are under development. Aerobic glycolysis in cancer cells can lead to excessive lactate production, which in turn promotes lactylation and influences tumor cell behavior. Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors. Because lactate and lactylation are | | --- | --- | | KEYWORDS | important in cancer, further investigation of the mechanisms underlying lactate metabolism and lactylation, and the development of therapeutic strategies targeting these processes, are topics of increasing interest. This review describes current research on lactate metabolism and lactylation in BC, thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.
Lactate; lactylation; breast cancer; tumor metabolism; immunotherapy prognosis | Introduction Breast cancer (BC), a major public health challenge globally, is a life-threatening disease and a major cause of mortality in women1-4. BC also shows high heterogeneity, and aggressive and complex biological characteristics5,6 . Various treatments, such as immunotherapy, emerging targeted inhibitors, antibody-drug conjugates, nanoparticles (such as albumin-based, metal-based, lipid-based, polymer-based, and micelle-based nanoparticles), and therapeutics targeting BC stem cells, are available for treating BC7-10. However, effective treatment of BC faces numerous challenges, including the poor *These authors contributed equally to this work. Correspondence to: Jian Wu [E-mail: mwujianglinxing@163.com](E-mail: mwujianglinxing@163.com) ORCID ID: [https://orcid.org/0000-0003-0087-3744](https://orcid.org/0000-0003-0087-3744) Received April 7, 2025; accepted June 4, 2025; published online July 16, 2025. Available [at www.cancerbiomed.org](at www.cancerbiomed.org) ©2025 The Authors. Creative Commons Attribution-NonCommercial 4.0 International License prognosis and drug resistance associated with triple-negative BC (TNBC)11-13. Additionally, neglected self-examination and clinical breast screening often lead to diagnosis of BC in late stages14,15 . Recent progress in genomics has enhanced understanding of the molecular pathways involved in BC pathogenesis, and enabled the discovery of novel biomarkers for diagnosis and the development of targeted therapies. Continuing studies on BC epidemiology have further refined knowledge regarding screening practices, the implementation of adjuvant therapies, and evolving risk factors16,17 . Although the use of precision medicine has expanded therapeutic options for patients with BC, it has concurrently introduced new complexities in clinical management. Metabolic reprogramming has been extensively investigated in the context of cancer, and

FAQs

Why is lactate important in breast cancer biology?

Aerobic glycolysis in BC increases lactate production, which can activate signaling pathways such as HIF-1α. Lactate accumulation also acidifies the tumor microenvironment and can suppress immune activity while enhancing cancer cell immune escape and invasion.

What does lactylation refer to and why is it studied in breast cancer?

Lactylation is a recently identified post-translational protein modification with roles in regulating cellular functions and metabolic pathways. It can influence gene expression by affecting histone modification status, thereby impacting tumor-related gene programs.

How can targeting lactate metabolism be used therapeutically in breast cancer?

The review notes that targeting lactate production or its metabolic byproducts shows potential value as a therapeutic strategy. This may support the development of novel antitumor agents and innovative anti-BC therapies aimed at lactate-related processes.

Sep 23, 2026

Uploaded by McQueen