Clinical update on head and neck cancer: molecular biology and ongoing challenges

Abstract

Head and neck squamous cell carcinomas (HNSCCs) are an aggressive, genetically complex and difficult to treat group of cancers. In lieu of truly effective targeted therapies, surgery and radiotherapy represent the primary treatment options for most patients. But these treatments are associated with significant morbidity and a reduction in quality of life. Resistance to both radiotherapy and the only available targeted therapy, and subsequent relapse are common. Research has therefore focussed on identifying biomarkers to stratify patients into clinically meaningful groups and to develop more effective targeted therapies. However, as we are now discovering, the poor response to therapy and aggressive nature of HNSCCs is not only affected by the complex alterations in intracellular signalling pathways but is also heavily influenced by the behaviour of the extracellular microenvironment. The HNSCC tumour landscape is an environment permissive of these tumours’ aggressive nature, fostered by the actions of the immune system, the response to tumour hypoxia and the influence of the microbiome. Solving these challenges now rests on expanding our knowledge of these areas, in parallel with a greater understanding of the molecular biology of HNSCC subtypes. This update aims to build on our earlier 2014 review by bringing up to date our understanding of the molecular biology of HNSCCs and provide insights into areas of ongoing research and perspectives for the future.

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation

“…As expected, outcomes and survival curves differ according to stage (Supplementary Figure 2). Tumor volume data as determined by delineation on RT planning CT images were available for 166 patients with a median volume of 23.2 cm 3 . Not all patients finished chemotherapy, but 126 patients (63%) received a cumulative dose of and above 200 mg/m 2 body surface area.…”

“…Cure and locoregional failure rates of around 50 and 25%, respectively, facilitate the evaluation of biological determinants of radiation response. Using biological characteristics of the tumors, outcome association studies revealed many potential determinants of prognosis and treatment response in HNSCC (3)(4)(5)(6)(7). This study evaluates complementarity and hierarchy of radiation response determining "HNSCC biology.…”

Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma

“…The heterogeneous nature of HNSCC calls for various treatment approaches [35]. Recent developments towards understanding the HNSCC disease have led to identify various targets and to develop the corresponding targeted therapies [36]. EGFR-targeted therapies, such as antisense gene therapy, monoclonal antibodies, and tyrosine kinase inhibitors, were first approved for HNSCC treatment [11,14].…”

Identification of PGRMC1 as a Candidate Oncogene for Head and Neck Cancers and Its Involvement in Metabolic Activities

“…As a strong correlation between PGRMC1 expression and tumor progression has been confirmed, it has become a novel and promising target of the therapeutic intervention for cancer treatments. Head and neck squamous cell carcinoma (HNSC) is one of the most common types of human cancer, with an annual incidence of more than 500,000 cases worldwide (Leemans et al, 2018;Alsahafi et al, 2019). Despite surgery, radiation, and chemotherapy, approximately half of all patients will die of the disease (Bratman et al, 2016).…”