ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 23 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- NN-01-195, a Novel Conjugate of HSP90 and AURKA Inhibitors, Effectively Targets Solid Tumors.Molecular cancer therapeutics · 2026Article
- Inhibition of primary ciliogenesis enhances efficacy of EGFR‑TKIs against non‑small cell lung cancer cells.Oncology reports · 2026Article
- Analysis of Primary Cilium-Bearing Human Neuroprogenitors Using Flow Cytometry.Stem cells international · 2026Article
- IFT139 regulates Hedgehog signaling and cilia structure through ciliary protein localization.Biology open · 2025Article
- Post-Translational Modifications in Cilia and Ciliopathies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Primary cilia-associated signalling in squamous cell carcinoma of head and neck region.Frontiers in oncology · 2024Review
- Article
- Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex.mBio · 2023Article
- Review
- Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma.Neuro-oncology · 2023Article
- Patterns of Ciliation and Ciliary Signaling in Cancer.Reviews of physiology, biochemistry and pharmacology · 2023Review
- Hedgehog signaling underlying tendon and enthesis development and pathology.Matrix biology : journal of the International Society for Matrix Biology · 2022Review
- Intraflagellar Transport Proteins as Regulators of Primary Cilia Length.Frontiers in cell and developmental biology · 2021Review
- Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease.Cellular signalling · 2020Review
- Restoration of primary cilia in obese adipose-derived mesenchymal stem cells by inhibiting Aurora A or extracellular signal-regulated kinase.Stem cell research & therapy · 2019Article
- Aurora Kinases as Therapeutic Targets in Head and Neck Cancer.Cancer journal (Sudbury, Mass.)Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
purposeFor many tumors, signaling exchanges between cancer cells and other cells in their microenvironment influence overall tumor signaling. Some of these exchanges depend on expression of the primary cilium on nontransformed cell populations, as extracellular ligands including Sonic Hedgehog (SHH), PDGFRα, and others function through receptors spatially localized to cilia. Cell ciliation is regulated by proteins that are themselves therapeutic targets. We investigated whether kinase inhibitors of clinical interest influence ciliation and signaling by proteins with ciliary receptors in cancer and other cilia-relevant disorders, such as polycystic kidney disease (PKD). EXPERIMENTAL
designWe screened a library of clinical and preclinical kinase inhibitors, identifying drugs that either prevented or induced ciliary disassembly. Specific bioactive protein targets of the drugs were identified by mRNA depletion. Mechanism of action was defined, and activity of select compounds investigated.
resultsWe identified multiple kinase inhibitors not previously linked to control of ciliation, including sunitinib, erlotinib, and an inhibitor of the innate immune pathway kinase, IRAK4. For all compounds, activity was mediated through regulation of Aurora-A (AURKA) activity. Drugs targeting cilia influenced proximal cellular responses to SHH and PDGFRα.
conclusionsThese results suggest a paradigm by which targeted drugs may have unexpected off-target effects in heterogeneous cell populations
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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.