Post-translational modifications in triple-negative breast cancer: research status and translation challenges.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 amplification. The lack of therapeutic targets contributes to its poor prognosis and limited treatment options. Nowadays, there is growing evidence that post-translational modifications (PTMs) play important roles in shaping the aggressive nature, immune microenvironment, and metabolic pathways in many tumor types. Here, in this review, we comprehensively summarized the roles of key PTMs, including phosphorylation, ubiquitination, acetylation, protein methylation, SUMOylation, lactylation, glycosylation, β-hydroxybutyrylation, and succinylation in TNBC. We discussed detection technologies for each PTM, detailed their molecular mechanisms and biological functions, and suggested therapeutic strategies targeting these modifications. Moreover, we reviewed PTM crosstalk networks and their clinical implications. Finally, we discussed the translational challenges and propose solutions for developing PTM-based diagnostics and therapies for TNBC. An evidence stratification framework was applied to grade the strength of the reviewed findings, distinguishing mechanistically validated, correlative, and clinically actionable evidence.