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Targeting palmitoylation: A novel frontier in cancer biology and immunotherapy

Ye Yang1, Enqi Zhang1, Xuanli Mao1

  • 1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Second Clinical Hospital of Wuhan University, Wuhan 430071, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|December 9, 2025
PubMed

Insights

Protein palmitoylation regulates cancer by altering metabolism, signaling, and immune evasion. Inhibiting this process shows promise for cancer therapy and immunotherapy, though challenges remain for clinical use.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Protein palmitoylation, the addition of palmitic acid to proteins, is a key post-translational modification.
  • It dynamically regulates protein function, localization, and stability, impacting cellular processes.
  • Aberrant palmitoylation is increasingly recognized as a driver of tumor development and progression.

Purpose of the Study:

  • To review the multifaceted roles of protein palmitoylation in cancer biology.
  • To highlight its influence on metabolic reprogramming, oncogenic signaling, and immune modulation.
  • To discuss current therapeutic strategies targeting palmitoylation and future directions.

Main Methods:

  • Literature review synthesizing current research on protein palmitoylation in cancer.
  • Analysis of multi-omics data and advanced detection technologies (mass spectrometry, imaging).
  • Evaluation of preclinical data for small-molecule inhibitors targeting palmitoylation.

Main Results:

  • Palmitoylation regulates key cancer pathways (AKT-mTOR, Wnt/β-catenin) and stabilizes immune checkpoints (PD-L1, TIM-3).
  • Dysregulated lipid metabolism contributes to aberrant palmitoylation in tumors.
  • Inhibitors of palmitoylation demonstrate preclinical efficacy in reducing tumor growth and enhancing immunotherapy.

Conclusions:

  • Protein palmitoylation is a critical regulator of tumor growth, metastasis, and immune evasion.
  • Targeting palmitoylation pathways offers a promising therapeutic avenue for cancer treatment.
  • Further research is needed to overcome challenges in selectivity, toxicity, and resistance for clinical translation.
Keywords:
Immune checkpointsPalmitoylationTargeted therapyTumor metabolismTumor microenvironmentZDHHC

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