ArticleNature communications2025
Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- KIF18A inhibitor prevents chromosomally unstable osteosarcoma growth by activating spindle assembly checkpoint.Cancer biology & therapy · 2026Article
- KIF18A knockdown enhances oxidative phosphorylation, suggesting a metabolic basis for antiviral activity against influenza A virus.Genes & genomics · 2026Article
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Kinesins in Cancer Drug Resistance: Mechanisms, Therapeutic Targeting, and Translational Potential.Cancers · 2026Review
- Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small Cell Lung Cancer.Cancer research communications · 2026Article
- Tetraploids or polyploid giants: who is truly dangerous?Trends in cell biology · 2026Review
- Incorporation of Organosilicon Motifs in Natural and Synthetic Small Molecules for Anticancer Therapeutics: Current Perspectives and Future Opportunities in Drug Design.Molecules (Basel, Switzerland) · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Molecular and Cell Biological Characterization of Patient-Derived Head and Neck Squamous Carcinoma Cell Lines.Cancer science · 2026Article
- KIF18A Maintains Kinetochore-Microtubule Attachments in CIN Cells by Limiting Microtubule Polymerization.bioRxiv : the preprint server for biology · 2026Article
- Impact of Chromosomal Instability and Aneuploidy in Cancer Development.Annual review of cancer biology · 2026Article
- Investigating the Consequences of Aneuploidy in Cancer and Normal Tissue.Advances in experimental medicine and biology · 2026Review
- Genomics of gastroesophageal junction adenocarcinomas and the Siewert classification.Translational gastroenterology and hepatology · 2026Article
- KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C.Cell reports · 2025Article
- Tumor aneuploidy as a prognostic and predictive biomarker in immune checkpoint blockade.Nature genetics · 2025Review
- Article
- Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025Article
- Article
- Leveraging Kinesin Family as Key Regulators of Malignant Progression and the Immunometabolic Niche for Precision Oncology.Technology in cancer research & treatmentReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells. Knockdown of KIF18A leads to mitotic defects and reduction of tumor growth. Screening of a chemical library for inhibitors of KIF18A enzymatic activity identified a hit that was optimized to yield VLS-1272, which is orally bioavailable, potent, ATP non-competitive, microtubule-dependent, and highly selective for KIF18A versus other kinesins. Inhibition of KIF18A's ATPase activity prevents KIF18A translocation across the mitotic spindle, resulting in chromosome congression defects, mitotic cell accumulation, and cell death. Profiling VLS-1272 across >100 cancer cell lines demonstrates that the specificity towards cancer cells with chromosome instability differentiates KIF18A inhibition from other clinically tested anti-mitotic drugs. Treatment of tumor xenografts with VLS-1272 results in mitotic defects leading to substantial, dose-dependent inhibition of tumor growth. The strong biological rationale, robust preclinical data, and optimized compound properties enable the clinical development of a KIF18A inhibitor in cancers with high chromosomal instability.
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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.