Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance - PubMed
8 days ago
- #treatment resistance
- #lactylation modification
- #hepatocellular carcinoma
- Hepatocellular carcinoma (HCC) has high global morbidity and mortality, with advanced HCC relying on systemic therapies.
- Primary and acquired drug resistance in HCC severely limits patient survival, necessitating new therapeutic targets.
- Lactylation modification, a novel post-translational modification mediated by lactate, plays a key role in HCC drug resistance.
- Lactylation modifies histones and non-histones, regulating gene expression and contributing to malignant progression and treatment resistance.
- Key resistance mechanisms include lactylated IGF2BP3 activating PCK2-NRF2, ALDOA lactylation enhancing stem cell self-renewal, and MOESIN lactylation in Tregs weakening anti-PD-1 efficacy.
- HCC tissues exhibit higher lactylation levels than normal tissues, correlating with poor prognosis.
- Lactylation-related genes and models can predict treatment responses in HCC.
- Therapeutic strategies like 2-DG, AZD3965, or SIRT3 activators can reverse lactylation and restore drug sensitivity.
- Despite limited specific detectors, lactylation is a promising target to overcome HCC drug resistance and aid precision treatment.