ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Radiation Enhancement of Head and Neck Squamous Cell Carcinoma by the Dual PI3K/mTOR Inhibitor PF-05212384.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Transcriptomic analysis of lncRNA-miRNA-mRNA competing endogenous RNA regulatory networks in radiation-induced mouse thymic degeneration.Immunologic research · 2026Article
- CCL5 improves radiation resistance through activation of the AMPK/mTOR pathway in adenoid cystic carcinoma.Journal of translational medicine · 2026Article
- Irradiation‑induced cellular senescence is linked to pro‑survival signaling and checkpoint regulation in a 2D and 3D model for head and neck cancer.Oncology reports · 2025Article
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Triple‑negative breast cancer cells that survive ionizing radiation exhibit an Axl‑dependent aggressive radioresistant phenotype.Experimental and therapeutic medicine · 2023Article
- Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes.International journal of oncology · 2023Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC).Cell death and differentiation · 2023Article
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Targeting Epithelial-to-Mesenchymal Transition in Radioresistance: Crosslinked Mechanisms and Strategies.Frontiers in oncology · 2022Review
- Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function.Nature communications · 2021Article
- The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.Molecular biology reports · 2021Review
- Pharmacological Inhibition of HSP90 Radiosensitizes Head and Neck Squamous Cell Carcinoma Xenograft by Inhibition of DNA Damage Repair, Nucleotide Metabolism, and Radiation-Induced Tumor Vasculogenesis.International journal of radiation oncology, biology, physics · 2021Article
- Article
- PKI-587 enhances radiosensitization of hepatocellular carcinoma by inhibiting the PI3K/AKT/mTOR pathways and DNA damage repair.PloS one · 2021Article
- HPVTranslational oncology · 2021Review
- Dacomitinib and gedatolisib in combination with fractionated radiation in head and neck cancer.Clinical and translational radiation oncology · 2021Article
- Making radiation therapy more effective in the era of precision medicine.Precision clinical medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRadiation remains a mainstay for the treatment of nonmetastatic head and neck squamous cell carcinoma (HNSCC), a malignancy characterized by a high rate of PI3K/mTOR signaling axis activation. We investigated the ATP-competitive dual PI3K/mTOR inhibitor, PF-05212384, as a radiosensitizer in preclinical HNSCC models. EXPERIMENTAL
designExtent of radiation enhancement of two HNSCC cell lines (UMSCC1-wtP53 and UMSCC46-mtP53) and normal human fibroblast (1522) was assessed by in vitro clonogenic assay with appropriate target inhibition verified by immunoblotting. Radiation-induced DNA damage repair was evaluated by γH2AX Western blots with the mechanism of DNA double-strand break repair abrogation investigated by cell cycle analysis, immunoblotting, and RT-PCR. PF-05212384 efficacy in vivo was assessed by UMSCC1 xenograft tumor regrowth delay, xenograft lysate immunoblotting, and tissue section immunohistochemistry.
resultsPF-05212384 effectively inhibited PI3K and mTOR, resulting in significant radiosensitization of exponentially growing and plateau-phase cells with 24-hour treatment following irradiation, and variable radiation enhancement with 24-hour treatment before irradiation. Tumor cells radiosensitized to a greater extent than normal human fibroblasts. Postirradiation PF-05212384 treatment delays γH2AX foci resolution. PF-05212384 24-hour exposure resulted in an evident G1-S phase block in p53-competent cells. Fractionated radiation plus i.v. PF-05212384 synergistically delayed nude mice bearing UMSCC1 xenograft regrowth, with potential drug efficacy biomarkers identified, including pS6, pAkt, p4EBP1, and Ki67.
conclusionsTaken together, our results of significant radiosensitization both in vitro and in vivo validate the PI3K/mTOR axis as a radiation modification target and PF-05212384 as a potential clinical radiation modifier of nonmetastatic HNSCC.
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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.