PI3K/PTEN/AKT/mTOR polymorphisms: Association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab‐docetaxel

Pfisterer, Katharina; Fusi, Alberto; Klinghammer, Konrad; Knödler, Maren; Nonnenmacher, Anika; Keilholz, Ulrich

doi:10.1002/hed.23604

Cited by 22 publications

(26 citation statements)

References 34 publications

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“…The AKT family (AKT1-3) has been found to integrate extracellular signals in several cellular processes, including growth, proliferation, differentiation, migration and survival (28). Numerous studies have demonstrated that the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin pathway serves an essential role in apoptosis and is frequently activated in numerous types of human cancer, such as head and neck squamous cell carcinoma (29,30), prostate cancer (31), breast cancer (32) and colorectal cancer (33). Cancer cells have a higher proliferation rate compared with wild-type cells and frequently lose the ability to undergo apoptosis (18).…”

Section: Discussionmentioning

confidence: 99%

Identification of genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use

Zhao

et al. 2016

Oncology Letters

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The present study aimed to identify genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use. Microarray dataset GSE42023, including 10 tissue samples of tongue cancer from patients with a history of tobacco and/or alcohol use (habit group) and 11 tissue samples of non-habit-associated tongue cancer (non-habit group), were downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) between the habit and non-habit groups were identified using the Linear Models for Microarray Data software package. The enrichment functions and pathways of these genes were subsequently predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Transcription factors (TFs) and tumor-associated genes (TAGs) were selected from the DEGs using the Encyclopedia of DNA Elements database and the TAG database, respectively. Protein-protein interaction (PPI) networks for DEGs were constructed using Cytoscape. In addition, functional module analysis was performed using BioNet. This analysis identified 642 DEGs between the habit and non-habit groups, including 200 upregulated and 442 downregulated genes. The majority of upregulated DEGs were functionally enriched in the regulation of apoptosis and the calcium signaling pathway. The majority of downregulated DEGs were functionally enriched in fat cell differentiation and the adipocytokine signaling pathway. In addition, 31 TFs and 42 TAGs were identified from the DEGs. Furthermore, this analysis demonstrated that certain DEGs, including AKT serine/threonine kinase 1 (AKT1), E1A binding protein p300 (EP300), erb-b2 receptor tyrosine kinase 2 (ERBB2) and epiregulin (EREG), had high connectivity degrees in the PPI networks and/or functional modules. Overall, DEGs in a functional module, such as AKT1, EP300, ERBB2 and EREG, may serve important roles in the development of tongue cancer in patients with a history of tobacco and/or alcohol use. These DEGs are potential therapeutic targets for the treatment of tongue cancer in these groups.

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Section: Discussionmentioning

confidence: 99%

Identification of genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use

Zhao

et al. 2016

Oncology Letters

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“…This raises the possibility that single mutations in the PI3K pathway may be responsible for SCCHN formation whereas multiple mutations in the pathway components cause disease progression. Indeed, a recent Phase II study determined whether genetic variations in the genes for PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (mTOR) were associated with differences in disease progression, survival, and response to therapy in a cohort of patients with recurrent and/or metastatic SCCHN treated with docetaxel plus cetuximab [42]. They demonstrated a correlation between the single-nucleotide polymorphisms PTEN:rs12569998 and AKT2:rs8100018 and risk of progression and PFS.…”

Section: The Pi3k/akt/mtor Pathwaymentioning

confidence: 99%

Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

2015

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“…Pfisterer K et al . revealed that patients with variants of AKT2:rs8100018 had a higher risk of progression after docetaxel and cetuximab and experienced a shorter progression-free survival in squamous cell carcinomas of the head and neck 42 . However, in contrast to these results, our study found that patients with AKT2:rs8100018 variants had a lower risk of recurrence after receiving preoperative CRT followed by radical surgery and experienced a longer DFS.…”

Section: Discussionmentioning

confidence: 99%

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

Peng

Zhou

et al. 2018

J. Cancer

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Objective: Although preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC), the clinical efficacy differs among patients. This study was conducted to determine the association between genetic variations in the PI3K/PTEN/AKT/mTOR pathway and clinical outcomes in LARC patients.Methods: Sixteen tagging single-nucleotide polymorphisms (SNPs) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) were genotyped. The associations of these SNPs with tumor response to preoperative CRT, postoperative disease-free survival (DFS) and overall survival (OS) were identified. Crude odds ratios (ORs) and hazard ratios (HRs) were adjusted by age, sex, clinical stage, tumor differentiation, tumor location, cycles of preoperative chemotherapy and time interval from CRT completion to surgery.Results: In an analysis of 97 LARC patients, the G/T+G/G genotype of AKT1:rs2498804 was associated with an increased tumor response rate (adjusted OR = 2.909, 95% confidence interval (CI), 1.127-7.505, P = 0.027). At a median of 65.7 months of follow-up, the G/C+C/C genotype of AKT2:rs8100018 was associated with a reduced risk of postoperative recurrence (adjusted HR = 0.414; 95% CI, 0.187-0.914, P = 0.029). Patients carrying the G/C+C/C genotype in AKT2:rs8100018 presented a higher 5-year DFS rate than those with the wild-type genotype (79.2% vs. 62.3%, P = 0.038). None of the SNPs were significantly associated with pathological complete response (pCR) or 5-year OS.Conclusions: The current study indicates that genetic variations within the PI3K/ PTEN/AKT/mTOR signaling pathway are associated with the clinical outcomes of LARC patients undergoing preoperative CRT followed by radical surgery.

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PI3K/PTEN/AKT/mTOR polymorphisms: Association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab‐docetaxel

Abstract: We identified combined genotypes associated with outcome of HNSCC, which might have an impact for identification of a target population for cetuximab-docetaxel treatment. Results should be considered as an initial finding and warrant validation in larger clinical trials.

Cited by 22 publications

References 34 publications

Identification of genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use

Identification of genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use

Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

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

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