ArticleCancers2021
A Novel Salt Inducible Kinase 2 Inhibitor, ARN-3261, Sensitizes Ovarian Cancer Cell Lines and Xenografts to Carboplatin.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Structure-Activity Relationship Studies Resulting in the Identification of Potent and Selective Salt-Inducible Kinase Inhibitors.ACS medicinal chemistry letters · 2026Article
- Inhibition of SIK2 and SIK3 induces adaptive ER-phagy and creates a therapeutic vulnerability in ovarian cancer.Research square · 2026Article
- Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer.Nature immunology · 2026Article
- A Review of SIK2 in Ovarian Cancer: Function and Emerging Targeted Therapies.OncoTargets and therapy · 2026Review
- The Role of the Salt-inducible Kinases in the Endocrine Glands.Endocrinology · 2025Review
- Therapeutic Targeting in Ovarian Cancer: Nano-Enhanced CRISPR/Cas9 Gene Editing and Drug Combination Therapy.International journal of nanomedicine · 2025Review
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers.The Journal of clinical investigation · 2022Article
- Next steps in the early detection of ovarian cancer.Communications medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Salt-induced kinase 2 (SIK2) is a serine-threonine kinase that regulates centrosome splitting, activation of PI3 kinase and phosphorylation of class IIa HDACs, affecting gene expression. Previously, we found that inhibition of SIK2 enhanced sensitivity of ovarian cancer cells to paclitaxel. Carboplatin and paclitaxel constitute first-line therapy for most patients with ovarian carcinoma, producing a 70% clinical response rate, but curing <20% of patients with advanced disease. We have asked whether inhibition of SIK2 with ARN-3261 enhances sensitivity to carboplatin in ovarian cancer cell lines and xenograft models. ARN-3261-induced DNA damage and apoptosis were measured with γ-H2AX accumulation, comet assays, and annexin V. ARN-3261 inhibited growth of eight ovarian cancer cell lines at an IC50 of 0.8 to 3.5 µM. ARN-3261 significantly enhanced sensitivity to carboplatin in seven of eight ovarian cancer cell lines and a carboplatin-resistant cell line tested. Furthermore, ARN-3261 in combination with carboplatin produced greater inhibition of tumor growth than carboplatin alone in SKOv3 and OVCAR8 ovarian cancer xenograft models. ARN-3261 enhanced DNA damage and apoptosis by downregulating expression of survivin. Thus, a SIK2 kinase inhibitor enhanced carboplatin-induced therapy in preclinical models of ovarian cancer and deserves further evaluation in clinical trials.
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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.