Therapeutic Potential of Targeting the SUMO Pathway in Cancer

SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typical...

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Bibliographic Details
Published in:Cancers 2021-08, Vol.13 (17), p.4402
Main Authors: Kukkula, Antti, Ojala, Veera K, Mendez, Lourdes M, Sistonen, Lea, Elenius, Klaus, Sundvall, Maria
Format: Article
Language:English
Subjects:
Breast cancer
Cancer
Cell cycle
Clinical trials
Cytokines
DNA methylation
Drug resistance
Enzymes
Genomes
Genotype & phenotype
Hypoxia
Immune response
Localization
Molecular modelling
Patients
Phosphorylation
Physiology
Post-translation
Proteins
Review
SUMO protein
Therapeutic targets
Translation
Tumorigenesis
Ubiquitin
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Summary:SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13174402