A newly identified process called lactylation involves lactate modifying histones and proteins, influencing gene expression to promote tumor growth and immune evasion, especially in aggressive cancers like triple-negative breast cancer (TNBC).

High levels of lactylation are associated with a significantly worse survival rate—up to 3.5 times lower—in cancer patients, as it silences tumor suppressor genes and activates oncogenic pathways, creating a 'double-hit' effect in TNBC.

Research indicates that targeting lactylation and lactate pathways could offer promising therapeutic strategies, including repurposing existing drugs, developing imaging tracers, and creating liquid biopsies for early detection and monitoring.

Funding from Chinese national and regional grants supports ongoing efforts to translate these findings into clinical trials for lactylation inhibitors, aiming to improve outcomes for patients with difficult-to-treat cancers like TNBC.

The Warburg effect describes how cancer cells preferentially convert glucose to lactate, creating an acidic microenvironment that fosters metastasis and suppresses immune responses, underpinning the importance of lactate in tumor progression.

Analysis of over 120 studies shows that lactate-induced lactylation alters protein functions in cancer and immune cells, activating pathways that promote invasion, immune suppression, and angiogenesis.

Researchers have developed a 24-gene lactate metabolism signature to predict treatment responses and use MRI-based lactate measurements as biomarkers for tumor aggressiveness, aiding diagnosis and monitoring.

Experimental therapies combining lactate oxidase nanoparticles with PD-L1 siRNA have demonstrated a 68% reduction in tumor size in mouse models, highlighting potential for combined metabolic and immunotherapy approaches.

Future clinical strategies include repurposing metabolic drugs, developing lactylation-specific PET imaging, and creating liquid biopsies to detect early recurrence, with ongoing collaborations to advance these translational efforts.

Targeting lactate production through existing drugs like LDH inhibitors or developing new lactylation-specific agents offers promising avenues for more effective treatments, particularly for resistant cancers like TNBC.

Breast cancer remains the most common malignancy among women worldwide, with triple-negative breast cancer (TNBC) being especially resistant to current therapies due to limited targets and high relapse rates.

Overall, lactate actively promotes breast cancer progression by fueling tumor growth, modifying proteins via lactylation, and enabling immune evasion, especially in aggressive subtypes like TNBC.