Overview of current and future biologically based targeted therapies in head and neck squamous cell carcinoma

Matta, Ajay; Ralhan, Ranju

doi:10.1186/1758-3284-1-6

Cited by 104 publications

(101 citation statements)

References 55 publications

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“…Current standard treatments for head and neck squamous cell carcinoma (HNSCC) are multimodal, including surgery, radiotherapy and chemotherapy. Despite advances in multimodality therapies, long-term survival rates remain poor, between 40-50%, and further improvements in therapeutic strategies are needed, particularly in individuals with advanced-stage cancer (1)(2)(3)(4)(5). Thus, new strategies, such as molecular targeted therapies, are needed.…”

Section: Introductionmentioning

confidence: 99%

Livin enhances chemoresistance in head and neck squamous cell carcinoma

et al. 2017

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Abstract. The responsiveness of head and neck squamous cell carcinoma (HNSCC) to chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer cells is a major cause of chemoresistance. Livin, a member of the human inhibitors of apoptosis protein family, is highly expressed in various human cancer tissues and is associated with tumor progression and poor prognosis in human cancers. The aim of the present study was to evaluate the role of Livin in the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5-fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and PCI50 cells). Reverse transcription polymerase chain reaction and western blotting were performed to determine mRNA and protein expression levels. Cell viability and apoptosis assays were used to assess the functional effects of small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had different sensitivity to chemotherapeutic drugs. Livin knockdown significantly enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells. Livin knockdown induced apoptosis and enhanced chemotherapyinduced apoptosis to cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase compared with that in control cells after cisplatin, 5-FU, or docetaxel treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU and docetaxel. Although further investigations are required to support these findings, our results demonstrated that novel therapeutic strategies with combined use of siRNA targeting Livin and chemotherapeutic agents may have applications in the treatment of advanced HNSCC.

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Section: Introductionmentioning

confidence: 99%

Livin enhances chemoresistance in head and neck squamous cell carcinoma

et al. 2017

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“…Moreover, dose-limiting toxicity of these chemotherapeutic agents in cancer patients restricts their clinical utility. Molecular targeted therapy is seen as a desirable alternative to and/or augmentation of CT and, as a result, has garnered considerable current interests (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Small Interfering RNA Targeting 14-3-3ζ Increases Efficacy of Chemotherapeutic Agents in Head and Neck Cancer Cells

Matta

DeSouza

Ralhan

et al. 2010

Molecular Cancer Therapeutics

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Patients diagnosed in advanced stages of head and neck squamous cell carcinoma often show limited response to chemotherapeutic agents. Recently, we reported the overexpression of 14-3-3ζ protein in head and neck premalignant and cancer tissues using liquid chromatography-tandem mass spectrometry with isotopic labeling and revealed its significance as a prognostic marker using immunohistochemical analysis. In this study, we determined the potential of 14-3-3ζ as a therapeutic target for head and neck cancer. Small interfering RNA (siRNA) targeting 14-3-3ζ was used to downregulate its expression in head and neck cancer cells in culture. Cell cycle analysis showed that head and neck cancer cells transfected with siRNA targeting 14-3-3ζ showed G 2 -M arrest. These siRNA transfectants also showed increased cell death on treatment with any one of the following chemotherapeutic agents: cisplatin, 5-fluorouracil, paclitaxel, or doxorubicin in comparison with the no transfection controls. Flow cytometric analysis using propidium iodide staining showed increased sub-G 0 fraction in siRNA-transfected cells treated with any of these chemotherapeutic agents, suggesting cell death; in addition, Annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay revealed increased apoptosis. Taken together, our results strongly showed that downregulation of 14-3-3ζ expression may serve to improve the sensitivity of head and neck cancer cells to chemotherapeutic agents. Mol Cancer Ther; 9(10); 2676-88. ©2010 AACR.

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“…The PI3K/Akt/GSK3β pathway represents one such downstream signaling cascade following EGFR phosphorylation in HNSCC, where it is involved in tumor development and progression and likely plays a role in tumor resistance to radiotherapy and chemotherapy [5,43,44]. As seen in Figures 5C and 5E, pre-treatment with 80 μg/ml of RA in UM-SCC-6 cells decreased EGF-induced phosphorylation of Akt and GSK-3β ser9 by 56% and 54%, respectively.…”

Section: Ra Inhibits Egfr Phosphorylation and Abrogates Pi3k And Mapkmentioning

confidence: 82%

Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

Tumur¹,

Guerra²,

Yanni³

et al. 2015

J Cancer Sci Ther

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Objective: Active components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. Rosmarinic acid (RA), a phenolic compound in various herbal plants, is well-recognized for its anti-oxidant, anti-inflammatory, anti-proliferative properties in a variety of cell types. In this report, we describe a novel role for RA as an inhibitor of epidermal growth factor (EGF) stimulated signaling in HNSCC and propose a cellular reactive oxygen species (ROS)-mediated mechanism for the observed effects.Methods: Cellular growth, migration and reactive oxygen species (ROS) profiles were examined in RA-treated and untreated HNSCC cell lines (UM-SCC-6 and UM-SCC-10B) using the WST-1 viability assay, established in vitro migration assays, and the CM-H2DCFDA ROS assay, respectively. The influence of RA on EGF-stimulated phosphorylation and its downstream pathways was evaluated using Western-blotting techniques.Results: RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines. Furthermore, RA inhibited EGF-induced phosphorylation of the EGFR at tyrosine residues 992 and 845, which led to downregulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ ERK) pathways.Conclusions: This is the first report describing both growth-and motility-inhibitory roles for RA in HNSCC cells. Additionally, our study is the first to demonstrate that treatment with RA can reduce EGF-induced activation of PI3K/ Akt in tumor cells. The present data suggests that RA holds promise as a chemotherapeutic agent against HNSCC. a novel strategy to down-regulate EGFR signaling using the phenolic compound, rosmarinic acid. RosmarinicActive components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. One such food component, rosmarinic acid (RA), is a widely distributed phenolic compound in various herbal plants such as rosemary, sweet basil, sage, mint, and perilla (Figure 1) [10,11]. RA is regarded as a daily-consumed safe ingredient, due to its extensive use in the food industry for flavoring, but studies have also elucidated a medicinal role for RA, especially in regard to its anti-oxidant, and anti-inflammatory activities [12,13]. Furthermore, an emerging body of literature has also described the growth inhibitory and anti-invasion properties of RA in colon, skin, breast and ovarian cancers in vitro and/or in vivo [14][15][16][17][18][19], but the mechanisms underlying these effects are poorly understood. A chemopreventive role for RA in HNSCC has been described in 7,12-dimethylbenz (a) anthracene-induced hamster buccal pouch carcinogenesis [20], but a chemotherapeutic role for RA in the treatment of HNSCC has not yet been reported.Given the anti-oxidant properties attributed to RA, it is possible that RA's anti-tumor effects stem from its ability to combat oxidative stress in HNSCC. Oxidative ...

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Overview of current and future biologically based targeted therapies in head and neck squamous cell carcinoma

Cited by 104 publications

References 55 publications

Livin enhances chemoresistance in head and neck squamous cell carcinoma

Livin enhances chemoresistance in head and neck squamous cell carcinoma

Small Interfering RNA Targeting 14-3-3ζ Increases Efficacy of Chemotherapeutic Agents in Head and Neck Cancer Cells

Rosmarinic Acid Inhibits Cell Growth and Migration in Head and Neck Squamous Cell Carcinoma Cell Lines by Attenuating Epidermal Growth Factor Receptor Signaling

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