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Advances in Cancer Treatment by Targeting the Neddylation Pathway

Wenbin Gai1, Zhiqiang Peng2, Cui Hua Liu3

  • 1Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Medical College, Qingdao University, Qingdao, China.

Frontiers in Cell and Developmental Biology
|April 26, 2021
PubMed

Insights

The neddylation pathway, regulated by NEDD8 (neural precursor cell expressed developmentally down-regulated protein 8), is crucial in cancer progression. Inhibiting this pathway with MLN4924 offers a promising strategy for novel antitumor combination therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) is a ubiquitin-like protein regulating substrate function.
  • The primary targets of NEDD8 are cullin-RING E3 ligases.
  • Aberrant neddylation pathway activity correlates with various cancer progressions.

Purpose of the Study:

  • To review current anticancer strategies targeting the neddylation pathway.
  • To explore the combined applications of these strategies in cancer therapy.

Main Methods:

  • Literature review of recent advancements in neddylation pathway targeting.
  • Analysis of combination therapies involving neddylation inhibitors.

Main Results:

  • The neddylation pathway is a significant target for cancer treatment.
  • MLN4924, a NEDD8-activating enzyme (NAE) inhibitor, shows potential in preclinical studies.
  • Combination therapies involving neddylation pathway inhibition are under investigation.

Conclusions:

  • Targeting the neddylation pathway presents a viable approach for developing new anticancer drugs.
  • Combined therapeutic strategies hold promise for enhanced antitumor efficacy.
Keywords:
MLN4924cancerdevelopmental down-regulation protein 8 (NEDD8)neddylationtreatment

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