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Abstract
Simple SummaryNext-generation sequencing of head and neck squamous cell carcinoma has revealed multiple new gene mutations, while simultaneously confirming the role of others in head and neck cancer tumorigenesis. The ever-expanding number of actionable druggable targets has fuelled a plethora of clinical trials assessing various pharmacotherapeutics in the management of this group of cancers. This review paper summarizes the state of play of molecular therapies used in head and neck oncology with particular focus dedicated to current FDA-approved drugs and emerging therapies undergoing advanced clinical trials.Head and neck cancer affects nearly 750,000 patients, with more than 300,000 deaths annually. Advances in first line surgical treatment have improved survival rates marginally particularly in developed countries, however survival rates for aggressive locally advanced head and neck cancer are still poor. Recurrent and metastatic disease remains a significant problem for patients and the health system. As our knowledge of the genomic landscape of the head and neck cancers continues to expand, there are promising developments occurring in molecular therapies available for advanced or recalcitrant disease. The concept of precision medicine is underpinned by our ability to accurately sequence tumour samples to best understand individual patient genomic variations and to tailor targeted therapy for them based on such molecular profiling. Not only is their purported response to therapy a factor of their genomic variation, but so is their inclusion in biomarker-driven personalised medicine therapeutic trials. With the ever-expanding number of molecular druggable targets explored through advances in next generation sequencing, the number of clinical trials assessing these targets has significantly increased over recent years. Although some trials are focussed on first-line therapeutic approaches, a greater majority are focussed on locally advanced, recurrent or metastatic disease. Similarly, although single agent monotherapy has been found effective in some cases, it is the combination of drugs targeting different signalling pathways that seem to be more beneficial to patients. This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in this area while also summarising ongoing efforts to bring more molecular therapies into clinical practice.
Highlights
The druggable genome is defined as the altered genes or gene products that can interact with molecules exhibiting therapeutic properties [1,2]
KIF1A, a kinesin, was identified as a novel head and neck squamous cell carcinoma (HNSCC) driver gene. Though, this analysis identified that 71% of the 502 HNSCC samples in the dataset had potentially actionable mutations, but that only 16% had a druggable mutation at any stage of development from preclinical to U.S Food and Drug Administration (FDA)-approved at time of publication
This paper summarises current and emerging molecular therapies in head and neck oncology driven by our understanding of gene mutations and genomic oncological pathways relevant to head and neck cancers
Summary
The druggable genome is defined as the altered genes or gene products that can interact with molecules exhibiting therapeutic properties [1,2]. KIF1A, a kinesin, was identified as a novel HNSCC driver gene Though, this analysis identified that 71% of the 502 HNSCC samples in the dataset had potentially actionable mutations (either SNPs/Indels, CNVs or all), but that only 16% had a druggable mutation at any stage of development from preclinical to U.S Food and Drug Administration (FDA)-approved at time of publication. The generally poor outcomes for head and neck cancers continue to drive innovation in targeted therapeutic approaches, repurposing of currently available pharmacotherapeutics, and clinical trials to test safety, efficacy and potential combination therapies Understanding of these current and emerging therapies for HNSCC necessitates a sound understanding of the signaling pathways involved in these cancers. Trials with reported outcomes in the literature are addressed in more detail than those still ongoing or terminated
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