Novel and Emerging Chemotherapeutic Agents in Head and Neck Cancer

The role of chemotherapy in the management of head and neck squamous cell cancers continues to evolve. Concurrent chemotherapy and radiation represents a standard treatment option for organ preservation in larynx and hypopharynx squamous cell carcinomas, unresectable locally advanced head and neck cancer, nasopharyngeal cancer, and post-operative therapy of high-risk resected disease. Chemotherapeutic agents and their combinations have known activity in metastatic disease and are frequently used for palliation. Emerging therapeutic approaches have been fueled by the observed shift in the pattern of disease recurrence after definitive therapy and the development of molecular targeted agents with disease activity. The recognition of human papillomavirus-associated oropharyngeal squamous cell carcinoma as a distinct clinical entity among head and neck cancers will influence the design of future clinical investigation.

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Soy Isoflavone Genistein Impedes Cancer Stemness and Mesenchymal Transition in Head and Neck Cancer through Activating miR-34a/RTCB Axis

Nutrients ◽

10.3390/nu12071924 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1924 ◽

Cited By ~ 1

Author(s):

Pei-Ling Hsieh ◽

Yi-Wen Liao ◽

Chang-Wei Hsieh ◽

Pei-Ni Chen ◽

Cheng-Chia Yu

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Epithelial Mesenchymal Transition ◽

Inhibitory Effect ◽

Chemotherapeutic Agents ◽

Tumor Initiating Cells ◽

Mesenchymal Transition ◽

Repressive Effect

Genistein, a soy-derived phytoestrogen, has been shown to exhibit anti-neoplastic activities in various cancers. Nevertheless, its effects on the elimination of tumor-initiating cells of head and neck cancer (HNC-TICs) remain unclear. Here, we investigated the inhibitory effect of genistein on HNC-TICs and potential mechanisms. Our results demonstrated that genistein lowered the proliferation of HNC-TICs by examining the percentage of ALDH1+ or CD44+ cells. Aside from the downregulation of epithelial-mesenchymal transition (EMT) in HNC-TICs, genistein restricted their tumor propagating capacities in a dose-dependent fashion. Moreover, genistein potentiated cell death caused by three commonly used chemotherapeutic agents (doxorubicin, cisplatin, and 5-FU). Our findings proved that genistein induced ROS production through upregulation of miR-34a, leading to apoptosis in HNC-TICs. The genistein-elicited miR-34a reduced self-renewal, migration, invasion capacities and ALDH1 activity, which may be partly owing to the repression of EMT. Furthermore, we showed that RTCB was a novel target that was negatively regulated by miR-34a and involved in the tumor repressive effect of genistein. Besides, the in vivo study validated that genistein retarded tumor growth through the elevation of miR-34a and suppression of RTCB. These results suggested that genistein-induced miR-34a contributed to the ROS-associated apoptosis and diminished stemness properties via repression of RTCB in HNC-TICs.

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Implantable Venous Access Device: Use in Patients with Advanced Head and Neck Cancer

Otolaryngology ◽

10.1177/019459988809900607 ◽

1988 ◽

Vol 99 (6) ◽

pp. 578-583 ◽

Cited By ~ 6

Author(s):

Benjamin Gruber ◽

William J. Moran ◽

Everett E. Vokes ◽

Thomas J. Dobleman ◽

Gary Y. Shaw ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Head And Neck Carcinoma ◽

Venous Access ◽

Chemotherapeutic Agents ◽

Advanced Head ◽

Infusion Chemotherapy ◽

Device Use ◽

Venous Access Device

As a result of prolonged hospitalizations and the frequent administration of sclerosing antibiotics and/or chemotherapeutic agents, vascular access frequently becomes difficult in patients with advanced head and neck carcinoma. Eighty-six totally implantable venous access devices were placed in 83 patients with advanced head and neck cancer to facilitate the administration of continuous intravenous infusion chemotherapy. Complications relating to surgical placement or usage of the device occurred in 29 of 86 ports (34%), leading to the removal of eight devices (9%). The implantation of two devices required revision. There were no serious sequelae from any of the complications. The port facilitated the administration of home chemotherapy in 11 patients. Because of our favorable experience, we now routinely recommend placement of these devices to all patients with advanced head and neck cancer at ourinstitution.

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An effective and well-tolerated strategy in recurrent and/or metastatic head and neck cancer: successive lines of active chemotherapeutic agents

BMC Cancer ◽

10.1186/1471-2407-14-504 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 12

Author(s):

Julien Péron ◽

Valentine Polivka ◽

Sylvie Chabaud ◽

Marc Poupart ◽

Philippe Ceruse ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Chemotherapeutic Agents

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mTOR Pathway and mTOR Inhibitors in Head and Neck Cancer

ISRN Otolaryngology ◽

10.5402/2012/953089 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Wei Gao ◽

John Zeng Hong Li ◽

Jimmy Yu Wai Chan ◽

Wai Kuen Ho ◽

Thian-Sze Wong

Keyword(s):

Head And Neck Cancer ◽

Targeted Therapy ◽

Head And Neck ◽

Neck Cancer ◽

Xenograft Model ◽

Mtor Inhibitors ◽

Chemotherapeutic Agents ◽

Therapeutic Effects

Head and neck cancer is the sixth most common type of Cancer worldwide. Since conventional treatment regimens are nonselective and are associated with systemic toxicities, intense investigations focus on molecular targeted therapy with high selectivity and low adverse effects. mTOR signaling pathway has been found to be activated in head and neck cancer, making it attractive for targeted therapy. In addition, expression levels of mTOR and downstream targets eIF4E, 4EBP1, S6K1, and S6 are potential diagnostic and prognostic biomarkers for head and neck cancer. mTOR inhibitors, such as rapamycin and its derivatives temsirolimus and everolimus, exhibit inhibitory effects on head and neck cancer in both in vitro cell line model and in vivo xenograft model. A large number of clinical trials have been initiated to evaluate the therapeutic effects of mTOR inhibitors on patients with head and neck cancer. mTOR inhibitor has potential as a single therapeutic agent or in combination with radiation, chemotherapeutic agents, or other targeted therapeutic agents to obtain synergistic repression on head and neck cancer.

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Antioxidative assessment of new trans palladium(II) complexes in head and neck cancer

Otolaryngologia Polska ◽

10.5604/01.3001.0013.3216 ◽

2019 ◽

Vol 73 (4) ◽

pp. 1-5

Author(s):

Katarzyna Malinowska ◽

Dariusz Kaczmarczyk ◽

Radosław Zajdel ◽

Anna Merecz-Sadowska ◽

Jurek Olszewski ◽

...

Keyword(s):

Head And Neck Cancer ◽

Antioxidant Enzymes ◽

Head And Neck ◽

Neck Cancer ◽

Treatment Strategies ◽

Biological Properties ◽

Economic Benefits ◽

Chemotherapeutic Agents ◽

Control Group ◽

Malignant Neoplasms

Background: The head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. The chemotherapy has limited use due to the tumor biological properties (in majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in the treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, use of low molecular weight complexes Pd(II) have the potential to be more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: The increases level of antioxidant enzymes were seen in blood sample from patients with head and neck cancer after incubation with Pd(II) complex.. For that group we obtained statistically significant result p = <0.001 Discussion: That project may contribute to the development of new more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and make therapy more effectiveness through reduce treatment expenses.

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Use of DNA repair pathway analysis to predict overall survival in head and neck cancer patients treated with TFHX chemoradiotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.6033 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 6033-6033

Author(s):

T. Seiwert ◽

D. T. Weaver ◽

X. Wang ◽

J. Kutok ◽

E. Cohen ◽

...

Keyword(s):

Overall Survival ◽

Dna Repair ◽

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Excision Repair ◽

Chemotherapeutic Agents ◽

Tumor Cell Death ◽

Survival Group ◽

Repair Pathways

6033 Background: Concurrent chemoradiotherapy is a standard-of-care for head and neck cancer. Radiotherapy and chemotherapeutic agents damage DNA; lack of adequate repair induces tumor cell death. The network of DNA repair pathways was examined to predict TFHX chemoradiotherapy outcomes. Methods: Biopsy specimens (paraffin) from 60 HNC patients were evaluated from tissue microarrays. Samples originated from patient groups from phase I/II studies: 1) poor-prognosis radiation-naïve, 2) re-irradiation. All were treated with TFHX-based chemoradiotherapy. DNA repair biomarkers XPF, pMK2, PAR, pH2AX, FANCD2, ATM, BRCA1, RAD51, ERCC1 (clone 8F1), and p53 were explored using IHC, automated image processing, and machine reading (>500 cells/read), for nuclear and cytoplasmic quantity, area, and intensity, and correlated with clinical outcome. Results: There was low inter-core variability per tumor with median patient ranking signal to noise ratio of 15.0 across all markers. Patients were stratified into short and long survival groups by determination of critical marker thresholds. Five DNA repair biomarkers (RAD51, ATM, BRCA1, XPF, FANCD2) exhibited univariate significance for overall survival (p = 2.65e-3, 1.53e-2, 4.77e-4, 8.57e-5, 1.32e-3)(additional clinical parameters multivariate analysis was not feasible due to sample size). ERCC1 was not statistically significant (p = 1.0). Pairwise biomarker combinations improved survival group discrimination. Combination of 4 DNA repair biomarkers (FANCD2, BRCA1, ATM, XPF) was also significant (p = 1.31e-4). Discriminant analysis demonstrated higher fractions of correctly identified patients in good/poor survival groups from four-marker tests. Conclusions: Five DNA repair biomarkers predicted overall survival following TFHX-based chemoradiotherapy. By contrast ERCC1 (8F1) was not significant. Combination of markers improved predictive ability in this study. The analysis of DNA repair pathways, particularly in homologous recombination, DNA damage response, and nucleotide excision repair, may be clinically useful. Validation in a larger, homogeneous patient population, and using platinum-based chemoradiotherapy, is indicated and currently ongoing. [Table: see text]

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