DeCure for Head and neck carcinoma

Recent new approaches to the treatment of head and neck cancer

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and affects 50,000 Americans annually. During the past 20 years, treatments for HNSCC have changed dramatically due largely to the advent of novel approaches such as combined modality therapy, as well as improvements in surgical and radiotherapeutic techniques. Ongoing advances in the multidisciplinary management of this complex and multivariate disease process are resulting in improved function, quality of life and survival. Here, we review state-of-the-art therapy and presents selected advances in the treatment of head and neck cancer.

Combined effects of Lapatinib and Cisplatin on colony formation of head and neck squamous cell carcinoma

AbstractBACKGROUND: Lapatinib targets human epidermal growth factor-receptor (EGFR) and Her2/neu receptor tyrosine-kinases and hence is under investigation in multimodal therapy concepts of advanced head and neck squamous cell carcinoma (HNSCC). We studied combined effects of lapatinib and cisplatin on colony formation (CF) of epithelial cells of individual HNSCC in short term ex vivo assays. MATERIALS AND METHODS: Biopsies of HNSCC were minced, collagenase-digested and exposed to serial lapatinib dilutions or solvent control (DMSO). The same lapatinib concentrations were tested in mixture with 1.67 μM, 3.33 or 6.67 μM cisplatin. After α 72-h incubation, adherent cells were ethanol-fixed and epithelial cells were stained using a Cy2™-labeled pan-cytokeratin antibody; then fluorescent colonies were counted. RESULTS: 33 of 51 ex vivo growing HNSCC (64.7%) exhibited epithelial CF allowing for cut-off detection. Lowest cut-off (complete chemotherapeutical suppressed CF) was noted at 6.25 μM lapatinib in three HNSCC (9.1%). The percentage of HNSCC achieving cut-off by 6.67 μM cisplatin (21.2%) was raised by addition of lapatinib at 6.25, 12.5, and 25 μM up to 33%, 45.5%, and 60.6%, respectively. However, we observed significant inter-individual different dose-response curves of HNSCC in response to lapatinib, e.g. variation in concentrations inhibiting CF to 50% (IC(50)) was 60-fold. At the individual level, antagonism, additivity, and synergism were detected as appropriate models describing the mode of action of cisplatin and lapatinib mixtures. CONCLUSION: Lapatinib suppresses CF of epithelial HNSCC cells, and in combination with cisplatin its efficacy is increased. However, caution is advisable due to significant heterogeneity in the response of HNSCC to lapatinib alone and when combined with cisplatin.

Complications of Head and Neck Surgery

AbstractThe management of carcinoma of the head and neck can be associated with significant morbidity or mortality. However, vigorous measures are required to cure or salvage the patient with a tumor. Complications of head and neck surgery are reviewed in an attempt to reacquaint the surgeon with measures required in dealing more effectively with head and neck malignancies.

Molecular genetics of head and neck cancer (Review)

AbstractUnderstanding of molecular regulatory pathways presents a novel therapeutic approach for the treatment of head and neck cancer. These specific check points are becoming the targeted therapeutic approach. In this review, we highlight certain major signaling mechanisms, which are involved in the pathophysiology of head and neck cancer. Also, we discuss the current ongoing trials based on the in vitro success of targeted therapies.

AbstractThe current review indicated that there are several genes and pathways that exhibit substantially altered expression in cancerous versus noncancerous states across studies. Further investigation into the genomic, proteomic, and functional consequences of these gene expression alterations may provide insight into the pathophysiology of head and neck squamous cell carcinoma.

Current status of genetics for prediction, prognosis, and gene therapy

AbstractThis article reviews recent studies that increase our understanding of the molecular pathogenesis of head and neck cancer and precancer and illustrates how this information can be used to make predictions about outcome for these patients. The ways in which this new technology can be harnessed to investigate the factors responsible for the changing pattern of clinical disease are also discussed. The final section of this article outlines the potential for using gene transfer techniques as a pharmacological adjuvant to destroy head and neck cancer and minimal residual disease.

A Randomised, Double-Blind, Placebo-Controlled, Multi-centre, Phase III Study of Post-Operative Adjuvant Lapatinib or Placebo and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib or Placebo Monotherapy in High-Risk Subjects With Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN)

AbstractThis is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial comparing the efficacy of adjuvant oral lapatinib versus placebo in high-risk subjects with head and neck cancer following surgery. Lapatinib or placebo will be administered post-operatively in combination with chemoradiotherapy followed by maintenance with lapatinib or placebo for 1 year. The primary goal is to determine if lapatinib is effective at reducing the recurrence of the disease in these high-risk patients.