Radioresistance in Head and Neck Squamous Cell Carcinoma — Possible Molecular Markers for Local Recurrence and New Putative Therapeutic Strategies

Ganci, Federica; Sacconi, Andrea; Manciocco, Valentina; Spriano, Giuseppe; Fontemaggi, Giulia; Carlini, Paolo; Blandino, Giovanni

doi:10.5772/60081

Cited by 10 publications

(17 citation statements)

References 123 publications

(175 reference statements)

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“…[30][31][32][33] One such example is represented by inhibitors targeting proteins in the PI3K/mTOR pathway (Table 1); the activation of this axis is one the main mechanisms of acquired radioresistance in head and neck squamous cell carcinoma patients and their inhibitors have emerged as a promising therapeutic approach for head and neck squamous cell carcinoma. 3,31,32 In agreement with these data, some of the identified genetic perturbations leading to the deregulation of the miRNA-related gene signature are proteins (eg KDR, FGFR1, K-RAS, STAT6, CDK4, and SRC) involved in the activation of the PI3K-mTOR Figure 7 Histologically tumor-free mucosa from head and neck squamous cell carcinoma patients is prone to the modulation of miRNAs expression. (a) Unsupervised clustering analysis representing the expression of the four prognostic miRNAs of normal tissue specimens from 21 head and neck squamous cell carcinoma patients cultured with conditioned medium from Cal27 cells or with control RPMI 10% fetal bovine serum medium (RPMI).…”

Section: Dl-pdmpmentioning

confidence: 55%

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Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Ganci¹,

Sacconi²,

Manciocco³

et al. 2017

Modern Pathology

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Head and neck squamous cell carcinoma is typically characterized by a high incidence of local recurrences. It has been extensively shown that mucosa from head and neck squamous cell carcinoma patients carries both genetic and gene expression alterations, which are mostly attributable to major etiologic agents of head and neck squamous cell carcinoma. We previously identified a signature of microRNAs (miRNAs) whose high expression in tumors is predictive of recurrence. Here, we investigated whether the deregulation of miRNA expression in the tumor-surrounding mucosa is correlated to disease recurrence. Specifically, comparing the miRNA expression in matched tumoral, peritumoral, and normal tissues collected from head and neck squamous cell carcinoma patients, we identified 35 miRNAs that are deregulated in both tumoral and peritumoral tissues as compared with normal matched samples. Four of these composed a miRNA signature that predicts head and neck squamous cell carcinoma local recurrence independently from prognostic clinical variables. The predictive power of the miRNA signature increased when using the expression levels derived from both the peritumoral and the tumoral tissues. The expression signal of the miRNAs composing the predictive signature correlated with the transcriptional levels of genes mostly associated with proliferation. Our results show that expression of miRNAs in tumor-surrounding mucosa may strongly contribute to the identification of head and neck squamous cell carcinoma patients at high risk of local recurrence.

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Section: Dl-pdmpmentioning

confidence: 55%

“…As a consequence, locoregional failure is the most common cause of death in head and neck squamous cell carcinoma patients. 3 Typically, the treatment consists of surgical resection followed by ionizing radiation or chemoradiation. The goal of surgical treatment is complete eradication of the primary tumor with a 'safe margin'.…”

mentioning

confidence: 99%

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Ganci¹,

Sacconi²,

Manciocco³

et al. 2017

Modern Pathology

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“…Most studies have also demonstrated a lower local control after radiation of tumors overexpressing EGFR. The protein overexpression is thought to result from enhanced transcription, whereas gene amplification has been observed less frequently [30, 32]. Stimulation of this receptor may activate many downstream molecules, such as PI3K (phosphatidylinositol-3-kinase) and RAS.…”

Section: Radioresistance In Head and Neck Cancermentioning

confidence: 99%

“…TP53 is a tumor suppressor gene which is a key regulator of genome stability through the modulation of DNA damage response. About 40–70% of HNSCC has mutation in TP53 gene, leading to inactivation of its protein product [ 30 , 33 ]. Alteration in p53 leads to an impaired capability of cell cycle arrest and to inhibition of the apoptosis.…”

Section: Radioresistance In Head and Neck Cancermentioning

confidence: 99%

“…Alteration in p53 leads to an impaired capability of cell cycle arrest and to inhibition of the apoptosis. As a consequence, tumor cells carrying TP53 mutation are less sensitive to radiation-induced cell death and are unable to restore DNA integrity, thus accumulating several genetic mutations which lead to increased tumor heterogeneity and finally to resistance to conventional radiotherapy [ 3 , 30 ]. Moreover, several evidences suggest that it is necessary to distinguish carefully TP53 mutations, which are related to the prognosis in HNSCC.…”

Section: Radioresistance In Head and Neck Cancermentioning

confidence: 99%

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MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

et al. 2017

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Resistance to the ionizing radiation is a current problem in the treatment and clinical management of various cancers including head and neck cancer. There are several biological and molecular mechanisms described to be responsible for resistance of the tumors to radiotherapy. Among them, the main mechanisms include alterations in intracellular pathways involved in DNA damage and repair, apoptosis, proliferation, and angiogenesis. It has been found that regulation of these complex processes is often controlled by microRNAs. MicroRNAs are short endogenous RNA molecules that posttranscriptionally modulate gene expression and their deregulated expression has been observed in many tumors including head and neck cancer. Specific expression patterns of microRNAs have also been shown to predict prognosis and therapeutic response in head and neck cancer. Therefore, microRNAs present promising biomarkers and therapeutic targets that might overcome resistance to radiation and improve prognosis of head and neck cancer patients. In this review, we summarize the current knowledge of the functional role of microRNAs in radioresistance of cancer with special focus on head and neck cancer.

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Role of microRNAs in metastasis, recurrence, and chemoradiation resistance of head and neck cancer

Dhamodharan,

Munirajan

2024

Diagnostic, Prognostic, and Therapeutic Role of MicroRNAs in Head and Neck Cancer

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Radioresistance in Head and Neck Squamous Cell Carcinoma — Possible Molecular Markers for Local Recurrence and New Putative Therapeutic Strategies

Cited by 10 publications

References 123 publications

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

Role of microRNAs in metastasis, recurrence, and chemoradiation resistance of head and neck cancer

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