Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy

Area of Science:

• Biochemistry
• Cancer Biology
• Epigenetics

Background:

• Cancer stemness drives tumor recurrence, metastasis, and therapy resistance.
• Tumor metabolism and epigenetic regulation are key modulators of cancer stemness.
• Lactylation links metabolism and epigenetics, emerging as a critical driver of cancer stemness.

Purpose of the Study:

• To systematically evaluate how lactylation orchestrates the cancer stem cell (CSC) landscape.
• To summarize the regulatory network of lactylation in cancer.
• To identify therapeutic strategies targeting lactylation for cancer treatment.

Main Methods:

• Systematic evaluation of lactylation's role in CSC functions.
• Analysis of the lactylation regulatory network, including enzymes and modulators.
• Review of preclinical data and clinical translation challenges.

Main Results:

• Lactylation influences CSC self-renewal, stemness-associated signaling, microenvironmental adaptation, and lineage plasticity.
• A dynamic regulatory network governing lactylation in cancer has been summarized.
• Promising therapeutic targets and preclinical successes in targeting lactylation were identified.

Conclusions:

• Lactylation is a critical driver of cancer stemness, linking metabolism and epigenetics.
• Targeting the metabolic-epigenetic circuitry of CSCs via lactylation holds therapeutic potential.
• Addressing challenges in clinical translation is crucial for combating therapy resistance and metastasis.