ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Genetic variants in the PI3K/PTEN/AKT/mTOR pathway predict head and neck cancer patient second primary tumor/recurrence risk and response to retinoid chemoprevention.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association of mTOR polymorphisms with cancer risk and clinical outcomes: a meta-analysis.PloS one · 2014Pooled it
- γ-Tocotrienol inhibits HeLa cell proliferation likely via modulation of the PI3K/AKT/mTOR signaling pathway.Frontiers in nutrition · 2026Article
- Causal effects of retinol and vitamin D on tongue cancer risk: a mendelian randomization study.BMC oral health · 2025Article
- Chemoprevention of Head and Neck Cancer: A Review of Current Approaches and Future Perspectives.Cancer prevention research (Philadelphia, Pa.) · 2024Review
- Sustained Oncogenic Signaling in the Cytostatic State Enables Targeting of Nonproliferating Persistent Cancer Cells.Cancer research · 2022Article
- High sensitive detection of circulating tumor cell by multimarker lipid magnetic nanoparticles and clinical verifications.Journal of nanobiotechnology · 2019Article
- Oncoproteomic and gene expression analyses identify prognostic biomarkers for second primary malignancy in patients with head and neck squamous cell carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Article
- Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery.Journal of Cancer · 2018Article
- Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.Scientific reports · 2016Article
- Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects.International journal of molecular sciences · 2016Review
- An endothelial TLR4-VEGFR2 pathway mediates lung protection against oxidant-induced injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Retinoids and rexinoids in cancer prevention: from laboratory to clinic.Seminars in oncology · 2016Review
- Retinoid Chemoprevention: Who Can Benefit?Current pharmacology reports · 2015Article
- Chemoprevention of head and neck squamous cell carcinoma through inhibition of NF-κB signaling.Oral oncology · 2014Review
- A GG allele of 3'-side AKT1 SNP is associated with decreased AKT1 activation and better prognosis of gastric cancer.Journal of cancer research and clinical oncology · 2014Article
- Systems biology of cisplatin resistance: past, present and future.Cell death & disease · 2014Review
- Headway and hurdles in the clinical development of dietary phytochemicals for cancer therapy and prevention: lessons learned from vitamin A derivatives.The AAPS journal · 2014Review
- Estimate of the accelerated proliferation by protein tyrosine phosphatase (PTEN) over expression in postoperative radiotherapy of head and neck squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2013Article
- Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway.Journal of biophotonics · 2013Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
purposeThe development of second primary tumors (SPT) or recurrence alters prognosis for curatively treated head and neck squamous cell carcinoma (HNSCC) patients. The 13-cis-Retinoic acid (13-cRA) has been tested as a chemoprevention agent in clinical trials with mixed results. Therefore, we investigated whether genetic variants in the PI3K/PTEN/AKT/mTOR pathway could serve as biomarkers to identify which patients are at high risk of an SPT/recurrence, while also predicting response to 13-cRA chemoprevention. EXPERIMENTAL
designA total of 137 pathway single-nucleotide polymorphisms were genotyped in 440 patients from the Retinoid Head and Neck Second Primary Trial and assessed for SPT/recurrence risk and response to 13-cRA. Risk models were created based on epidemiology, clinical, and genetic data.
resultsTwenty-two genetic loci were associated with increased SPT/recurrence risk, with six also being associated with a significant benefit following chemoprevention. Combined analysis of these high-risk/high-benefit loci identified a significant (P = 1.54 × 10(-4)) dose-response relationship for SPT/recurrence risk, with patients carrying four to five high-risk genotypes having a 3.76-fold [95% Confidence Interval (CI), 1.87-7.57] increase in risk in the placebo group (n = 215). Patients carrying four to five high-risk loci showed the most benefit from 13-cRA chemoprevention, with a 73% reduction in SPT/recurrence (95% CI, 0.13-0.58) compared with those with the same number of high-risk genotypes who were randomized to receive placebo. Incorporation of these loci into a risk model significantly improved the discriminatory ability over models with epidemiology, clinical, and previously identified genetic variables.
conclusionsThese results show that loci within this important pathway could identify individuals with a high-risk/high-benefit profile and are a step toward personalized chemoprevention for HNSCC patients.
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