ArticleCell reports2022
Activation of STAT3 through combined SRC and EGFR signaling drives resistance to a mitotic kinesin inhibitor in glioblastoma.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Review
- Type I interferon signaling defines a novel disease signature in xeroderma pigmentosum C human keratinocytes.Scientific reports · 2026Article
- An expanded role for single-cell chemical genomics profiling in drug discovery.The Biochemical journal · 2026Review
- Quinazolinone derivatives as potential anti‑tumor agents: Structural features and molecular mechanisms in inducing cell death (Review).International journal of molecular medicine · 2025Review
- Identifying regulators of aged fibroblast activation in 3D tissue models.Scientific reports · 2025Article
- Berberine: a promising strategy to combat cetuximab-resistance in colorectal cancer.BMC cancer · 2025Article
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.Journal of neuro-oncology · 2025Review
- Baricitinib in chronic kidney disease: an exploratory analysis integrating network toxicology, molecular docking and pharmacovigilance.Frontiers in medicine · 2025Article
- Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence.iScience · 2024Article
- A Repurposed Drug Selection Pipeline to Identify CNS-Penetrant Drug Candidates for Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2024Article
- EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.Neuro-oncology · 2024Article
- Antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly.Molecular biology of the cell · 2024Article
- Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma.Cell reports · 2024Article
- Eg5 and Diseases: From the Well-Known Role in Cancer to the Less-Known Activity in Noncancerous Pathological Conditions.Biochemistry research international · 2024Review
- Chemoresistant fibroblasts dictate neoadjuvant chemotherapeutic response of head and neck cancer via TGFα-EGFR paracrine signaling.NPJ precision oncology · 2023Article
- Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma.bioRxiv : the preprint server for biology · 2023Article
- Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.The Journal of clinical investigation · 2023Article
- Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Inhibitors of the mitotic kinesin Kif11 are anti-mitotics that, unlike vinca alkaloids or taxanes, do not disrupt microtubules and are not neurotoxic. However, development of resistance has limited their clinical utility. While resistance to Kif11 inhibitors in other cell types is due to mechanisms that prevent these drugs from disrupting mitosis, we find that in glioblastoma (GBM), resistance to the Kif11 inhibitor ispinesib works instead through suppression of apoptosis driven by activation of STAT3. This form of resistance requires dual phosphorylation of STAT3 residues Y705 and S727, mediated by SRC and epidermal growth factor receptor (EGFR), respectively. Simultaneously inhibiting SRC and EGFR reverses this resistance, and combined targeting of these two kinases in vivo with clinically available inhibitors is synergistic and significantly prolongs survival in ispinesib-treated GBM-bearing mice. We thus identify a translationally actionable approach to overcoming Kif11 inhibitor resistance that may work to block STAT3-driven resistance against other anti-cancer therapies as well.
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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.