ArticleCell systems2019
VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells.
Article in Cell systems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- The MTH1 inhibitor TH287 sensitized Castration-Resistant Prostate Cancer cells to ionizing radiation therapy.International urology and nephrology · 2026Article
- PAIRWISE: Deep Learning-based Prediction of Effective Personalized Drug Combinations in Cancer.Research square · 2026Article
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Unraveling disulfidptosis for prognostic modeling and personalized treatment strategies in lung adenocarcinoma.Future science OA · 2024Article
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option.Frontiers in cell and developmental biology · 2024Review
- Article
- Plk1 Inhibitors and Abiraterone Synergistically Disrupt Mitosis and Kill Cancer Cells of Disparate Origin Independently of Androgen Receptor Signaling.Cancer research · 2023Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress.Oncogene · 2022Article
- TH588 and Low-Dose Nocodazole Impair Chromosome Congression by Suppressing Microtubule Turnover within the Mitotic Spindle.Cancers · 2021Article
- MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.Cancer research · 2021Article
- Identification of novel microtubule inhibitors effective in fission yeast and human cells and their effects on breast cancer cell lines.Open biology · 2021Article
- Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma.Scientific reports · 2021Article
- Discovering and validating cancer genetic dependencies: approaches and pitfalls.Nature reviews. Genetics · 2020Review
- Intrinsic and Extrinsic Factors Affecting Microtubule Dynamics in Normal and Cancer Cells.Molecules (Basel, Switzerland) · 2020Review
- SYNERGxDB: an integrative pharmacogenomic portal to identify synergistic drug combinations for precision oncology.Nucleic acids research · 2020Article
- Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent.Molecular cell · 2020Article
- AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma.Cell death and differentiation · 2020Article
- The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors.Molecular cancer therapeutics · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
There is an unmet need for new antimitotic drug combinations that target cancer-specific vulnerabilities. Based on our finding of elevated biomolecule oxidation in mitotically arrested cancer cells, we combined Plk1 inhibitors with TH588, an MTH1 inhibitor that prevents detoxification of oxidized nucleotide triphosphates. This combination showed robust synergistic killing of cancer, but not normal, cells that, surprisingly, was MTH1-independent. To dissect the underlying synergistic mechanism, we developed VISAGE, a strategy integrating experimental synergy quantification with computational-pathway-based gene expression analysis. VISAGE predicted, and we experimentally confirmed, that this synergistic combination treatment targeted the mitotic spindle. Specifically, TH588 binding to β-tubulin impaired microtubule assembly, which when combined with Plk1 blockade, synergistically disrupted mitotic chromosome positioning to the spindle midzone. These findings identify a cancer-specific mitotic vulnerability that is targetable using Plk1 inhibitors with microtubule-destabilizing agents and highlight the general utility of the VISAGE approach to elucidate molecular mechanisms of drug synergy.
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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.