scholarly journals mTOR Pathway and mTOR Inhibitors in Head and Neck Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
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.

scholarly journals Correction: In Vitro and In Vivo Synergistic Antitumor Activity of the Combination of BKM120 and Erlotinib in Head and Neck Cancer: Mechanism of Apoptosis and Resistance

2020 ◽  
Vol 19 (9) ◽  
pp. 1955-1955
Author(s):  
Abu Syed Md Anisuzzaman ◽  
Abedul Haque ◽  
Dongsheng Wang ◽  
Mohammad Aminur Rahman ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Antitumor Activity ◽  
Head And Neck ◽  
Neck Cancer ◽  
Synergistic Antitumor Activity

PO-0942 EXPRESSION OF THE EGFR/HER2/PAKT PATHWAY IN VITRO AND IN VIVO IS AFFECTED BY HYPOXIA IN HUMAN HEAD AND NECK CANCER

2012 ◽  
Vol 103 ◽  
pp. S371
Author(s):  
J. Bussink ◽  
J.H.A.M. Kaanders ◽  
D.L. Wheeler ◽  
A.J. van der Kogel ◽  
M. Iida ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Human Head

Tyrosine kinase profiling guides combined therapeutic strategies in head and neck cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6078-6078
Author(s):  
R. Rodríguez-Barrueco ◽  
M. Ortíz-Ruiz ◽  
J. J. Cruz ◽  
A. Ocana ◽  
A. Pandiella
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cell Lines ◽  
Neck Cancer ◽  
Tyrosine Kinases ◽  
Egf Receptor ◽  
Drug Combinations ◽  
Metastatic Setting

6078 Background: Squamous cell carcinoma of the head and neck (SCCHN) is still an incurable disease in the metastatic setting. A particular subgroup of proteins implicated in the head and neck cancer are the tyrosine kinases (TK). Therapeutic inhibition of several of them including the EGF receptor with cetuximab in combination with radiotherapy or chemotherapy has shown to be clinically useful. Beyond EGFR, oncogenic activation of other TKs may be implicated in the genesis/progression of SCCHN. In this context, the identification of the TKs activated in SCCHN is a must in order to adequately target these kinases with already available inhibitors. Methods: Here we have investigated activated tyrosine kinases in head and neck cancer tumors derived from patients using a human phospho protein array for 42 receptor tyrosine kinases (RTK). Western-blot experiments were performed to validate each phospho RTK in tumors from patients. The same approach was followed in a series of head and neck cancer cell lines. In vivo xenografted models were used to study the antiproliferative effect of the combination of specific TK inhibitors against them. Results: TK receptors of the EGF and the VEGF family were the mostly activated in tumors derived from patients. 90% of patients revealed high pEGFR content. In addition, other EGFR/HER family receptors, such as HER3, were also activated (phosphorylated) in samples from patients. These data were corroborated in the SCCHN cell lines. In these cells, other RTK signalling intermediates were also active. Particularly, the Akt and FAK kinases. Combination of the anti-EGFR-HER2 TK inhibitor lapatinib with dasatinib (that targets FAK) was synergistic in vitro. Combination of lapatinib with the anti-VEGFR TK inhibitor pazopanib was inefficient in vitro, but resulted in a better trend in response in the in vivo xenografted models, as compared to the action of the single agents. Conclusions: Rational target drug combinations should be based on the identification of activated TK receptors or downstream signalling molecules. In head and neck cancer combination strategies using anti-EGFR/HER, anti-FAK, and anti-VEGFR compounds increases the action of individual treatments. These results open the door for future clinical development of these drug combinations. No significant financial relationships to disclose.

scholarly journals The Cancer Stem Cell Concept in Progression of Head and Neck Cancer

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Zhuo (Georgia) Chen
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Solid Tumors ◽  
Neck Cancer ◽  
Human Head ◽  
Short Review ◽  
Cancer Type ◽  
Progression Model

Human head and neck cancer (HNC) is a highly heterogeneous disease. Understanding the biology of HNC progression is necessary for the development of novel approaches to its prevention, early detection, and treatment. A current evolutional progression model has limitations in explaining the heterogeneity observed in a single tumor nest. Accumulating evidence supports the existence of cancer stem cells (CSCs) as small subpopulations in solid tumors, including HNC. These CSCs can be selected by appropriate cell surface markers, which are cancer type specific and have been confirmed by uniquein vitroandin vivoassays. Selected CSC populations maintain a self-renewal capability and show aggressive behaviors, such as chemoresistance and metastasis. In addition to introducing the CSC concept in solid tumors, this short review summarizes current publications in HNC CSC and the prospective development and application of the CSC concept to HNC in the clinic.

scholarly journals Pharmacodynamics of cisplatin in human head and neck cancer: correlation between platinum content, DNA adduct levels and drug sensitivity in vitro and in vivo

1998 ◽  
Vol 79 (1) ◽  
pp. 82-88 ◽  
Author(s):  
M J P Welters ◽  
A M J Fichtinger-Schepman ◽  
R A Baan ◽  
A J Jacobs-Bergmans ◽  
A Kegel ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Drug Sensitivity ◽  
Human Head ◽  
Dna Adduct ◽  
Platinum Content

scholarly journals In Vitro and In Vivo Synergistic Antitumor Activity of the Combination of BKM120 and Erlotinib in Head and Neck Cancer: Mechanism of Apoptosis and Resistance

2017 ◽  
Vol 16 (4) ◽  
pp. 729-738 ◽  
Author(s):  
Abu Syed Md Anisuzzaman ◽  
Abedul Haque ◽  
Dongsheng Wang ◽  
Mohammad Aminur Rahman ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Antitumor Activity ◽  
Head And Neck ◽  
Neck Cancer ◽  
Synergistic Antitumor Activity

scholarly journals Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors

1999 ◽  
Vol 42 (21) ◽  
pp. 4434-4445 ◽  
Author(s):  
David Zacheis ◽  
Arindam Dhar ◽  
Shennan Lu ◽  
Matora M. Madler ◽  
Jozef Klucik ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Retinoic Acid ◽  
Head And Neck ◽  
Cell Lines ◽  
Cancer Cell ◽  
Neck Cancer ◽  
Cancer Cell Lines ◽  
Retinoic Acid Receptors
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