Publications by authors named "Ezra Eddy Wyssam Cohen"

Background: Rapamycin is an mTOR inhibitor with preclinical efficacy in squamous cell carcinoma of the head and neck (SCCHN). However, mTOR inhibitors also increase Akt activity in SCCHN cell lines, which would promote survival and oncogenesis. Enzastaurin is an AGC kinase inhibitor with nanomolar inhibitory concentrations for Akt and protein kinase C (PKC).

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The number of targeted small molecules being developed in oncology is increasing rapidly. Many of these are designed to inhibit multiple kinases, and thus the mechanisms of responsiveness and predictive biomarkers can be difficult to discern. In fact, with few exceptions, multi-kinase inhibitors are developed with limited mechanism-based patient selection.

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Single agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have demonstrated reproducible response rates of 5-15% in treatment of squamous cell carcinomas of the head and neck (SCCHN). The subset of patients that benefits most from these agents remains unknown. We reviewed individual patient data from five clinical trials of erlotinib, lapatinib, or gefitinib to determine if there are clinical characteristics that are associated with clinical benefit defined as complete response (CR), partial response (PR), and stable disease (SD) >4months.

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Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that activates multiple signaling pathways, including phosphatidylinositol-3-kinase/v-AKT murine thymoma viral oncogene homolog protein (Akt), has long been a target of novel therapies. Despite universal EGFR expression in head and neck squamous cell carcinoma (HNSCC), the majority of patients do not respond to EGFR inhibitors. This review focuses on mechanisms of resistance to these agents in HNSCC, and how these may be unique when compared with other malignancies such as non-small cell lung and colorectal cancers.

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Protein kinase C (PKC) zeta has been implicated as a mediator of epidermal growth factor (EGF) receptor (EGFR) signaling in certain cell types. Because EGFR is ubiquitously expressed in squamous cell carcinomas of the head and neck (SCCHN) and plays a key role in tumor progression, we determined whether PKCzeta is required for tumor cell proliferation and viability. Examination of total and phosphorylated PKCzeta expression in normal oral mucosa, dysplasia, and carcinoma as well as SCCHN tumor cell lines revealed a significant increase in activated PKCzeta expression from normal to malignant tissue.

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