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Induction of anaplastic lymphoma kinase (ALK) as a novel mechanism of EGFR inhibitor resistance in head and neck squamous cell carcinoma patient-derived models.
Abstract Head and neck squamous cell carcinoma (HNSCC) currently only has one FDA-approved cancer intrinsic targeted therapy, the epidermal growth factor receptor (EGFR) inhibitor cetuximab, to which only approximately 10% of tumors are sensitive. In order to extend therapy options, we subjected patient-derived HNSCC cells to small-molecule inhibitor and siRNA screens, first, to find effective combination therapies with an EGFR inhibitor, and second, to determine a potential mechanistic basis for repurposing the FDA approved agents for HNSCC. The combinations of EGFR inhibitor with anaplastic lymphoma kinase (ALK)...
Source: Cancer Biology and Therapy - June 1, 2018 Category: Cancer & Oncology Authors: Ouyang X, Barling A, Lesch A, Tyner JW, Choonoo G, Zheng C, Jeng S, West TM, Clayburgh D, Courtneidge SA, McWeeney SK, Kulesz-Martin M Tags: Cancer Biol Ther Source Type: research

The FA/BRCA Pathway Identified as the Major Predictor of Cisplatin Response in Head and Neck Cancer by Functional Genomics
Patients with advanced stage head and neck squamous cell carcinoma (HNSCC) are often treated with cisplatin-containing chemoradiation protocols. Although cisplatin is an effective radiation sensitizer, it causes severe toxicity and not all patients benefit from the combination treatment. HNSCCs expectedly not responding to cisplatin may better be treated with surgery and postoperative radiation or cetuximab and radiation, but biomarkers to personalize chemoradiotherapy are not available. We performed an unbiased genome-wide functional genetic screen in vitro to identify genes that influence the response to cisplatin in HNS...
Source: Molecular Cancer Therapeutics - March 1, 2017 Category: Cancer & Oncology Authors: Martens-de Kemp, S. R., Brink, A., van der Meulen, I. H., de Menezes, R. X., te Beest, D. E., Leemans, C. R., van Beusechem, V. W., Braakhuis, B. J. M., Brakenhoff, R. H. Tags: Companion Diagnostics and Cancer Biomarkers Source Type: research

STAT1 and Cisplatin/Cetuximab in HNSCC
Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGF receptor (EGFR) inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefit from the use of these two drugs in combination. Possible explanations for this include overlapping downstream signaling cascades. Using in vitro studies, we tested the hypothesis that cisplatin and EGFR inhibitors rely on the activation of the tumor suppressor STAT1, characterized by its phosphorylation at s...
Source: Molecular Cancer Therapeutics - September 2, 2015 Category: Cancer & Oncology Authors: Schmitt, N. C., Trivedi, S., Ferris, R. L. Tags: Cancer Biology and Signal Transduction Source Type: research