p53-based therapeutics for head and neck squamous cell carcinoma

Tassone, Patrick; Old, Matthew; Teknos, Theodoros N.; Pan, Quintin

doi:10.1016/j.oraloncology.2013.03.447

Cited by 36 publications

(30 citation statements)

References 38 publications

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“…Since then, many attempts have been made to use adenoviral p53 to treat HNSCC in phase 1, 2, and 3 clinical trials. In many of those trials, adenoviral p53 alone or in combination with chemotherapy or radiotherapy produced tumor regression (Tassone et al, 2013). In spite of these encouraging results, the long-term effects of this adenovirus-mediated TP53 gene therapy still need to be tested in larger cohorts, and further improvements in gene delivery methods are required for safe, effective use of WT p53 gene therapy for HNSCC patients.…”

Section: Therapeutic Strategies For Hnscc With P53 Mutationsmentioning

confidence: 99%

TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response

Zhou

Liu

Myers³

2016

J of Cellular Biochemistry

278

240

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Recent studies describing the mutational landscape of head and neck squamous cell carcinoma (HNSCC) on a genomic scale by our group and others, including The Cancer Genome Atlas, have provided unprecedented perspective for understanding the molecular pathogenesis of HNSCC progression and response to treatment. These studies confirmed that mutations of the TP53 tumor suppressor gene were the most frequent of all somatic genomic alterations in HNSCC, alluding to the importance of the TP53 gene in suppressing the development and progression of this disease. Clinically, TP53 mutations are significantly associated with short survival time and tumor resistance to radiotherapy and chemotherapy in HNSCC patients, which makes the TP53 mutation status a potentially useful molecular factor for risk stratification and predictor of clinical response in these patients. In addition to loss of wild-type p53 function and the dominant-negative effect on the remaining wild-type p53, some p53 mutants often gain oncogenic functions to promote tumorigenesis and progression. Different p53 mutants may possess different gain-of-function properties. Therefore, mutant p53 is not just one protein but actually a variety of proteins that contribute to an exceptionally vast network of tumor-promoting processes. Herein we review the most up-to-date information about TP53 mutations available via The Cancer Genome Atlas-based analysis of HNSCC and discuss our current understanding of the potential tumor-suppressive role of p53, focusing on gain-of-function activities of p53 mutations. We also summarize our knowledge regarding use of the TP53 mutation status as a potential evaluation or stratification biomarker for prognosis and a predictor of clinical response to radiotherapy and chemotherapy in HNSCC patients. Finally, we discuss possible strategies for targeting HNSCCs bearing TP53 mutations.

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Section: Therapeutic Strategies For Hnscc With P53 Mutationsmentioning

confidence: 99%

TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response

Zhou

Liu

Myers³

2016

J of Cellular Biochemistry

278

240

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“…P53 gene mutation can be detected in about 50 percent of HNSCC patient samples [50, 51]. The incidence of p53 mutation significantly increased when the pre-malignant diseases progressed to invasive cancer [52, 53].…”

Section: Precision Medicine For Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

Toward the use of precision medicine for the treatment of head and neck squamous cell carcinoma

et al. 2016

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Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of “big data”, such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed.

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“…Mutation of the TP53 tumor suppressor gene is the most common and one of the earliest genetic alterations in head and neck squamous cell carcinoma (HNSCC), occurring in more than half of all cases (40,41), underscoring the importance of our finding. p53 is a tumor suppressor that regulates cell cycle progression and apoptosis in response to cellular stress, primarily DNA damage and genomic instability (42).…”

Section: Discussionmentioning

confidence: 61%

Expression of apoptosis-regulating miRNAs and target mRNAs in oral squamous cell carcinoma

et al. 2015

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p53-based therapeutics for head and neck squamous cell carcinoma

Cited by 36 publications

References 38 publications

TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response

TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response

Toward the use of precision medicine for the treatment of head and neck squamous cell carcinoma

Expression of apoptosis-regulating miRNAs and target mRNAs in oral squamous cell carcinoma

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