Molecular Pathways and Druggable Targets in Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck cancers are a heterogeneous group of neoplasms, affecting an ever increasing global population. Despite advances in diagnostic technology and surgical approaches to manage these conditions, survival rates have only marginally improved and this has occurred mainly in developed countries. Some improvements in survival, however, have been a result of new management and treatment approaches made possible because of our ever-increasing understanding of the molecular pathways triggered in head and neck oncogenesis, and the growing understanding of the abundant heterogeneity of this group of cancers. Some important pathways are common to other solid tumours, but their impact on reducing the burden of head and neck disease has been less than impressive. Other less known and little-explored pathways may hold the key to the development of potential druggable targets. The extensive work carried out over the last decade, mostly utilising next generation sequencing has opened up the development of many novel approaches to head and neck cancer treatment. This paper explores our current understanding of the molecular pathways of this group of tumours and outlines associated druggable targets which are deployed as therapeutic approaches in head and neck oncology with the ultimate aim of improving patient outcomes and controlling the personal and economic burden of head and neck cancer.

Mutational Profile of Human Papilloma Virus (HPV) Induced and Non-HPV Induced Head and Neck Squamous Cell Carcinoma

“…Phosphorylated MAPK translocates into the nucleus, phosphorylating various transcription factors that trigger the expression of distinct target genes, which advocates proliferation, differentiation, migration, invasion, angiogenesis and metastasis in HNSCC cells. Aberration of EGFR signal activation can bring about disruption of cancer cell homeostasis [57][58][59].…”

Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma

“…A Phase I immuno-radiotherapy with cetuximab and avelumab (Bavencio), a PD-L1 inhibitor, showed that cetuximab-RT plus avelumab is feasible in patients with advancedstage HNSCC who are not good candidates for cisplatin treatment. Tumour recurrence was 50% after a median of 12 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) months follow-up [244]. Patients are currently being recruited in a Phase I clinical trial to assess the feasibility of intratumoural administration of ipilimumab monotherapy prior to surgical resection, and to assess the immune system response to treatment (NCT02812524).…”

“…Understanding of these current and emerging therapies for HNSCC necessitates a sound understanding of the signaling pathways involved in these cancers. For this, readers are directed to earlier papers detailing the molecular landscape, oncological pathways and druggable targets for head and neck cancers [22,23]. This review is intended to act as a coherent comprehensive summary of current and emerging molecular therapies for head and neck cancers (HNC).…”

Candida albicans induces upregulation of programmed death ligand 1 in oral squamous cell carcinoma

“…Substantial expression of PD‐L1 could be observed in the keratinocytes of oral lichen planus (OLP) 10 and oral leukoplakia (OLK), 11 and the increased PD‐L1 level was positively correlated with the malignant transformation of OLK within 5 years 12 . In addition, some studies discussing the role of immune checkpoint biomarkers in OSCC also inferred that the expression of PD‐L1 in OSCC samples was correlated with increased progression and decreased survival rates, though more precise evidence is needed 9,13,14 …”

“…12 In addition, some studies discussing the role of immune checkpoint biomarkers in OSCC also inferred that the expression of PD-L1 in OSCC samples was correlated with increased progression and decreased survival rates, though more precise evidence is needed. 9,13,14 Previous studies showed that the infection of C. albicans could induce upregulation of PD-L1 on T cells and natural killer cells. 15,16 Besides, the pathogen-associated molecular patterns (PAMPs) and candidalysin of C. albicans could activate Toll-like receptors (TLR2/ TLR4) on innate immune cells 17 and epidermal growth factor receptor (EGFR) on oral epithelial cells, 18 respectively.…”