ArticleGut2022
Targeting pancreatic cancer by TAK-981: a SUMOylation inhibitor that activates the immune system and blocks cancer cell cycle progression in a preclinical model.
Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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The trial behind it
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Who cites it
93 citing papers in PubMed, 121 citations in OpenAlex.
- A First-In-Human Study of the SUMOylation Inhibitor Subasumstat in Patients with Advanced/Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies.Cancer research communications · 2025Trial
- SUMOylation inhibitor TAK-981 suppresses proliferation and induces apoptosis in SK-UT-1B uterine leiomyosarcoma cells.Oncology letters · 2026Article
- SUMOylation-stabilized G6PD orchestrates metabolic rewiring for oxidative stress survival and chemoresistance in HCC via a PKCδ-phosphorylation trigger.Cell death and differentiation · 2026Article
- Inhibition of Pax6 sumoylation suppresses the tumorigenicity of pancreatic cancer cells.Cell death and differentiation · 2026Article
- Immunomodulation of Pancreatic Cancer via Inhibition of SUMOylation and the CD155/TIGIT Pathway.Molecular cancer therapeutics · 2026Article
- SUMOylation in cancer: molecular mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Article
- SUMOylation Inhibitor TAK-981 Alleviates Hallmark Features of Preeclampsia Related to High Glucocorticoid Exposure by Inhibiting Placental Oxidative Stress in Rats.Antioxidants (Basel, Switzerland) · 2026Article
- Aberrant SUMOylation Restricts the Targetable Cancer Immunopeptidome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SAE1 emerges as a pan-cancer driver and key regulator of HCC metastasis.Journal of advanced research · 2026Article
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Chemical inhibition of SUMOylation activates the FSHD locus.Scientific reports · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Targeting SUMOylation Triggers IFN-β-dependent Activation of Patient and Allogenic NK Cells in Preclinical Models of Acute Myeloid Leukemia.Molecular cancer therapeutics · 2026Article
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- ML-792 impairsFrontiers in cellular and infection microbiology · 2026Article
- SERPINB3 enhances NPM1 sumoylation via inhibiting SENP3's activity and promotes lung tumorigenesis.Cell death & disease · 2025Article
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- TAK-981 potentiates doxorubicin immunocide in triple-negative breast cancer by IFN I-dependent NK cell stimulation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePancreatic ductal adenocarcinoma (PDAC) has the characteristics of high-density desmoplastic stroma, a distinctive immunosuppressive microenvironment and is profoundly resistant to all forms of chemotherapy and immunotherapy, leading to a 5-year survival rate of 9%. Our study aims to add novel small molecule therapeutics for the treatment of PDAC.
designWe have studied whether TAK-981, a novel highly selective and potent small molecule inhibitor of the small ubiquitin like modifier (SUMO) activating enzyme E1 could be used to treat a preclinical syngeneic PDAC mouse model and we have studied the mode of action of TAK-981.
resultsWe found that SUMOylation, a reversible post-translational modification required for cell cycle progression, is increased in PDAC patient samples compared with normal pancreatic tissue. TAK-981 decreased SUMOylation in PDAC cells at the nanomolar range, thereby causing a G2/M cell cycle arrest, mitotic failure and chromosomal segregation defects. TAK-981 efficiently limited tumour burden in the KPC3 syngeneic mouse model without evidence of systemic toxicity. In vivo treatment with TAK-981 enhanced the proportions of activated CD8 T cells and natural killer (NK) cells but transiently decreased B cell numbers in tumour, peripheral blood, spleen and lymph nodes. Single cell RNA sequencing revealed activation of the interferon response on TAK-981 treatment in lymphocytes including T, B and NK cells. TAK-981 treatment of CD8 T cells ex vivo induced activation of STAT1 and interferon target genes.
conclusionOur findings indicate that pharmacological inhibition of the SUMO pathway represents a potential strategy to target PDAC via a dual mechanism: inhibiting cancer cell cycle progression and activating anti-tumour immunity by inducing interferon signalling.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.