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Pharmacologically targeting protein lactylation to overcome cancer drug resistance

Yumin Wang1, Jinxia Chen2, Yan Wang3

  • 1Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, China.

European Journal of Medicinal Chemistry
|July 1, 2025
PubMed

Insights

Protein lactylation, a new modification, drives cancer drug resistance. Targeting lactylation regulators offers a promising strategy to overcome resistance to various cancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Drug resistance is a significant obstacle in cancer treatment.
  • Protein lactylation is an emerging post-translational modification linked to cancer drug resistance.

Purpose of the Study:

  • To review lactylation regulators (writers, erasers, readers) and their functions.
  • To summarize mechanisms of lactylation in modulating resistance to chemotherapy, immunotherapy, and targeted therapy.
  • To highlight emerging strategies involving pharmacological inhibition of lactylation to overcome cancer drug resistance.

Main Methods:

  • Literature review of recent advances in protein lactylation research.
  • Analysis of studies investigating lactylation's role in various cancer treatment modalities.
  • Synthesis of findings on lactylation regulators and their therapeutic targeting.

Main Results:

  • Identified key lactylation regulators and their involvement in cancer progression.
  • Detailed mechanisms by which lactylation confers resistance to diverse cancer treatments.
  • Summarized evidence for targeting lactylation to re-sensitize cancer cells to therapy.

Conclusions:

  • Protein lactylation is a critical mediator of cancer drug resistance.
  • Targeting lactylation pathways presents a viable therapeutic avenue for overcoming treatment failure.
  • Further research into lactylation is essential for developing novel anti-cancer strategies.
Keywords:
CancerDrug resistanceLactylationLactylation regulators

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