ArticlePLoS biology2023
Diverse microtubule-targeted anticancer agents kill cells by inducing chromosome missegregation on multipolar spindles.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03393741 (Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy), which is not on this map. Cited by 14 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.
Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Pretreatment Chromosomal Instability Correlates With Radiation Sensitivity in Squamous Cell Cancers.International journal of radiation oncology, biology, physics · 2026Article
- Prognostic, diagnostic and therapeutic value of the cancer tubulin code.Cancer metastasis reviews · 2026Review
- 2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression.Scientific reports · 2026Article
- Article
- Screening a living biobank identifies cabazitaxel as a strategy to combat acquired taxol resistance in high-grade serous ovarian cancer.Cell reports. Medicine · 2025Article
- Alternative Agents to Colcemid for Obtaining High-Quality Metaphase Spreads.Animals : an open access journal from MDPI · 2025Article
- Evolutionary adaptation to hyperstable microtubules selectively targets tubulins and is empowered by the spindle assembly checkpoint.Cell reports · 2025Article
- Small Molecules Identified by an In Silico Docking Screen Targeting Anaphase-Promoting Complex/Cyclosome Subunit 1 (APC1) Potentiate Paclitaxel-Induced Breast Cancer Cell Death.Molecules (Basel, Switzerland) · 2025Article
- Correction: Diverse microtubule-targeted anticancer agents kill cells by inducing chromosome missegregation on multipolar spindles.PLoS biology · 2025Article
- MAD1 upregulation sensitizes to inflammation-mediated tumor formation.PLoS genetics · 2024Article
- CENP-E Inhibition Induces Chromosomal Instability and Synergizes with Diverse Microtubule-Targeting Agents in Breast Cancer.Cancer research · 2024Article
- YY2/BUB3 Axis promotes SAC Hyperactivation and Inhibits Colorectal Cancer Progression via Regulating Chromosomal Instability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Suppressing Anaphase-Promoting Complex/Cyclosome-Cell Division Cycle 20 Activity to Enhance the Effectiveness of Anti-Cancer Drugs That Induce Multipolar Mitotic Spindles.International journal of molecular sciences · 2024Review
- The Causes and Consequences of DNA Damage and Chromosomal Instability Induced by Human Papillomavirus.Cancers · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Microtubule-targeted agents are commonly used for cancer treatment, though many patients do not benefit. Microtubule-targeted drugs were assumed to elicit anticancer activity via mitotic arrest because they cause cell death following mitotic arrest in cell culture. However, we recently demonstrated that intratumoral paclitaxel concentrations are insufficient to induce mitotic arrest and rather induce chromosomal instability (CIN) via multipolar mitotic spindles. Here, we show in metastatic breast cancer and relevant human cellular models that this mechanism is conserved among clinically useful microtubule poisons. While multipolar divisions typically produce inviable progeny, multipolar spindles can be focused into near-normal bipolar spindles at any stage of mitosis. Using a novel method to quantify the rate of CIN, we demonstrate that cell death positively correlates with net loss of DNA. Spindle focusing decreases CIN and causes resistance to diverse microtubule poisons, which can be counteracted by addition of a drug that increases CIN without affecting spindle polarity. These results demonstrate conserved mechanisms of action and resistance for diverse microtubule-targeted agents. Trial registration: clinicaltrials.gov, NCT03393741.
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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.