The role of cyclin‐dependent kinases in oral potentially malignant disorders and oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a major global health problem with a relatively low‐moderate 5‐year survival rate. OSCC is often preceded by lesions and conditions known as oral potentially malignant disorders (OPMDs) that have an increased risk of malignant transformation. Despite advances in diagnostic technology and cancer research, the prognosis of OSCC remains poor as it is frequently detected a late stage. Understanding the molecular pathways involved in oral carcinogenesis provides a platform to identify biomarkers that may allow the early detection of OSCC and accurate prediction of the malignant potential of OPMDs. In addition, specific molecular inhibitors can be developed to target these important pathways and allow advanced therapeutic management to improve the prognosis of this malignancy. A common feature across a number of different cancers is the dysfunction of cell cycle moderator proteins known as cyclin‐dependent kinases. This review summarises the current literature regarding the role of cyclin‐dependent kinases in oral carcinogenesis with a particular focus on cyclin‐dependent kinases 4 (CDK4) and 6 (CDK6). This is of particular relevance as CDK4 and CDK6 inhibitors have shown some promising results in other cancer types and are interesting potential treatments for OSCC.

Peroxiredoxin1 Knockdown Inhibits Oral Carcinogenesis via Inducing Cell Senescence Dependent on Mitophagy

“…40 CDK4 expression was obviously increased with grade of dysplastic oral leukoplakia. 39 In this study, we observed that the expression level of CDK2 and CDK6 was lower in Prx1 +/+ mouse tongue hyperplastic and dysplastic tissues than those in the OSCC tissues. Prx1 knockdown resulted in CDK2 and CDK6 expression decrease in the tongue hyperplastic and dysplastic tissues.…”

“…CDK2 and CDK6 overexpression can lead to tumor development, it was significantly correlated with tumor differentiation, invasion and metastasis. 38,39 CDK4 can be inhibited by p21 to prevent the phosphorylation of Rb and maintain cell stagnation in the G1 phase. 40 CDK4 expression was obviously increased with grade of dysplastic oral leukoplakia.…”

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

“…This kinase is a catalytic subunit of the protein kinase complex, important for G1 phase progression and G1/S cell cycle transition. CDK6 and CDK4, phosphorylate and thus regulate the activity of tumour suppressor Retinoblastoma protein, making CDK6 an important protein in cancer development [ 1 ].…”

“…Therefore, the diagnosis of HNC at early cancerous stages has become vitally important. A greater majority of HNC are squamous cell carcinomas (HNSCC) arising from the epithelial tissue of the oral cavity, pharynx and larynx [ 1 ]. Numerous genetic aberrations are involved in head and neck tumours.…”

“…Additionally, various environmental factors including HPV infection and tobacco and alcohol exposure are associated with HNSCCs. HNSCC is a highly heterogeneous tumour type, hence personalised patient management should be based on both patient and tumour features [ 1 ].…”