ArticleBritish journal of cancer2014
Rac1 as a potential therapeutic target for chemo-radioresistant head and neck squamous cell carcinomas (HNSCC).
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Rac1 GTPase Regulates the SCFCancers · 2026Article
- RAC1 regulates Sonic Hedgehog-medulloblastoma growth via GLI-mediated transcription.Neuro-oncology · 2026Article
- Overcoming acquired doxorubicin resistance of ovarian carcinoma cells by verapamil‑mediated promotion of DNA damage‑driven cytotoxicity.International journal of oncology · 2026Article
- RAC1 promotes the occurrence and development of tongue squamous cell carcinoma by regulating RAC1/PAK1/LIMK1 signaling pathway.Scientific reports · 2025Article
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- Diterpenoid fromInternational journal of molecular sciences · 2024Article
- Unique vulnerability of RAC1-mutant melanoma to combined inhibition of CDK9 and immune checkpoints.Oncogene · 2024Article
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
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- Critical pathways of oral squamous cell carcinoma: molecular biomarker and therapeutic intervention.Medical oncology (Northwood, London, England) · 2022Review
- Construction of a novel radiosensitivity- and ferroptosis-associated gene signature for prognosis prediction in gliomas.Journal of Cancer · 2022Article
- Identification of potent and novel inhibitors against RAC1: a Rho family GTPase.In silico pharmacology · 2022Article
- Article
- Skin Cancers and the Contribution of Rho GTPase Signaling Networks to Their Progression.Cancers · 2021Review
- RBM5-AS1 promotes radioresistance in medulloblastoma through stabilization of SIRT6 protein.Acta neuropathologica communications · 2021Article
- PI3k inhibitors (BKM120 and BYL719) as radiosensitizers for head and neck squamous cell carcinoma during radiotherapy.PloS one · 2021Article
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Rho GTPases in cancer radiotherapy and metastasis.Cancer metastasis reviews · 2020Review
- VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma.Nature communications · 2020Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundIn order to improve therapy for HNSCC patients, novel methods to predict and combat local and/or distant tumour relapses are urgently needed. This study has been dedicated to the hypothesis that Rac1, a Rho GTPase, is implicated in HNSCC insensitivity to chemo-radiotherapy resulting in tumour recurrence development.
methodsParental and radiation-resistant (IRR) HNSCC cells were used to support this hypothesis. All cells were investigated for their sensitivity to ionising radiation and cisplatin, Rac1 activity, its intracellular expression and subcellular localisation. Additionally, tumour tissues obtained from 60 HNSCC patients showing different therapy response were evaluated for intratumoral Rac1 expression.
resultsRadiation-resistant IRR cells also revealed resistance to cisplatin accompanied by increased expression, activity and trend towards nuclear translocation of Rac1 protein. Chemical inhibition of Rac1 expression and activity resulted in significant improvement of HNSCC sensitivity to ionising radiation and cisplatin. Preclinical results were confirmed in clinical samples. Although Rac1 was poorly presented in normal mucosa, tumour tissues revealed increased Rac1 expression. The most pronounced Rac1 presence was observed in HNSCC patients with poor early or late responses to chemo-radiotherapy. Tissues taken at recurrence were characterised not only by enhanced Rac1 expression but also increased nuclear Rac1 content.
conclusionsIncreased expression, activity and subcellular localisation of Rac1 could be associated with lower early response rate and higher risk of tumour recurrences in HNSCC patients and warrants further validation in larger independent studies. Inhibition of Rac1 activity can be useful in overcoming treatment resistance and could be proposed for HNSCC patients with primary or secondary chemo-radioresistance.
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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.