ArticleJournal of experimental & clinical cancer research : CR2015
Crizotinib-induced antitumour activity in human alveolar rhabdomyosarcoma cells is not solely dependent on ALK and MET inhibition.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Epithelioid and spindle rhabdomyosarcoma with TFCP2 rearrangement in abdominal wall: a distinctive entity with poor prognosis.Diagnostic pathology · 2023Pooled it
- Crizotinib- or Ceritinib-Conjugated Platinum(IV) Prodrugs As Potent Multiaction Agents Inducing Antiproliferative Effects in 2D and 3D Cancer Cell Models.Journal of medicinal chemistry · 2025Article
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- MAPK-targeted therapies in non-gastrointestinal stromal tumor soft tissue sarcomas: current landscape and future directions.Frontiers in oncology · 2025Review
- Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis.Oncogene · 2024Article
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Journal of clinical medicine · 2021Review
- Crizotinib induced antitumor activity and synergized with chemotherapy and hormonal drugs in breast cancer cells via downregulating MET and estrogen receptor levels.Investigational new drugs · 2021Article
- Combined crizotinib and endocrine drugs inhibit proliferation, migration, and colony formation of breast cancer cells via downregulation of MET and estrogen receptor.Medical oncology (Northwood, London, England) · 2021Article
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Cytoskeleton Dynamics in Peripheral T Cell Lymphomas: An Intricate Network Sustaining Lymphomagenesis.Frontiers in oncology · 2021Review
- Crizotinib sensitizes the erlotinib resistant HCC827GR5 cell line by influencing lysosomal function.Journal of cellular physiology · 2020Article
- Article
- The Receptor Tyrosine Kinase RON and Its Isoforms as Therapeutic Targets in Ewing Sarcoma.Cancers · 2020Article
- The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.Expert review of anticancer therapy · 2019Review
- Therapeutic Approaches Targeting PAX3-FOXO1 and Its Regulatory and Transcriptional Pathways in Rhabdomyosarcoma.Molecules (Basel, Switzerland) · 2018Review
- (S)-crizotinib reduces gastric cancer growth through oxidative DNA damage and triggers pro-survival akt signal.Cell death & disease · 2018Article
- A subgroup of pleural mesothelioma expresses ALK protein and may be targetable by combined rapamycin and crizotinib therapy.Oncotarget · 2018Article
- E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.Cancer discovery · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRhabdomyosarcoma (RMS) is the most commonly diagnosed malignant soft tissue tumour in children and adolescents. Aberrant expression of Anaplastic Lymphoma Kinase (ALK) and MET gene has been implicated in the malignant progression of RMS, especially in the alveolar subtype. This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied.
methodsRH4 and RH30 alveolar RMS (ARMS) cell lines were treated with crizotinib and then assessed by using proliferation, viability, migration and colony formation assays. Multiple approaches, including flow cytometry, immunofluorescence, western blotting and siRNA-based knock-down, were used in order to investigate possible molecular mechanisms linked to crizotinib activity.
resultsIn vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival. Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2. Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively. The accumulation of reactive oxygen species (ROS) seemed to contribute to crizotinib effects in RH4 and RH30 cells. Moreover, crizotinib-treated RH4 and RH30 cells exhibited a decreased migratory/invasive capacity and clonogenic potential.
conclusionsThese results provide a further insight into the molecular mechanisms affected by crizotinib in ARMS cells inferring that it could be a useful therapeutic tool in ARMS cancer treatment.
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