Emerging Therapies in the Treatment of Locally Advanced Squamous Cell Cancers of Head and Neck

Abstract

Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs.

Recurrent Oral Cancer: Current and Emerging Therapeutic Approaches

“…Activated EMT signaling pathways (e.g., activation of Wnt/β-catenin, PI3-K/AKT, MAPK, and Notch) is well documented to occur in advanced OCC (Boyer et al, 2000; Conacci-Sorrell et al, 2002; Nelson and Nusse, 2004; Larue and Bellacosa, 2005; Nawshad et al, 2005; Tommasi et al, 2007; Barker, 2008; Agarwal et al, 2010; Courtney et al, 2010; Falasca, 2010; Ihle and Powis, 2010; Wong et al, 2010). Preclinical studies also reported a significant correlation between EMT phenotype, drug resistance, and relapses (Zeisberg and Neilson, 2009) including in OCC patients (Machiels and Schmitz, 2011; Raza et al, 2011). …”

Network based identification of different mechanisms underlying pathogenesis of human papilloma virus‐active and human papilloma virus‐negative oropharyngeal squamous cell carcinoma

“…Our main goals are to find specific biomarkers for discriminating different types of OPSCC (HPV active and negative) and to propose potential targeted therapies specific for each group. Considering these two groups (HPV‐active and HPV‐negative), our study will focus only on biological processes underlying the “distinction” of the specified groups (and therefore giving insight to targeted therapy of OPSCC subtypes based on HPV activity); for example, EGFR or PI3K/AKT pathways, which are known as two important pathways (and therefore targets for therapies) in the pathogenesis of head and neck cancers, are not highlighted in our analysis because their behavior has not been observed to be significantly different in these groups . This study is composed of two main analyses: gene co‐expression network analysis and consensus network analysis.…”

An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer

“…Other targeted therapies remain under investigation in HNC, including antiangiogenic agents, PI3K/Akt/mTor inhibitors, and p53 gene replacement therapy. 58−60 Whereas such targeted approaches have certainly benefited some patients, their overall impact on HNC treatment has been mixed, 59−62 and personalized or combination therapy will likely prove necessary to maximize clinical success of these targeted drugs; 60,61 thus, more effective general first-line chemotherapy treatments are still much needed. Given the limited but promising data on the potential of MTAs in HNC, appropriate disease models therefore represent a useful context for the testing and development of new agents in the class.…”