The role of hypoxia in oral cancer and potentially malignant disorders: a review

Abstract

Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated 'potentially malignant disorders'. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia-induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena.

Propofol suppresses hypoxia‐induced esophageal cancer cell migration, invasion, and EMT through regulating lncRNA TMPO‐AS1/miR‐498 axis

“…22 Hypoxia exists in many solid tumor microenvironments. 23 In these tumor cells, hypoxia condition induced the increase of HIF-1α level, and thus regulated the expression of downstream genes, which led to the change of cell progression. 24,25 Previous evidence has revealed that propofol is capable of reversing the effect of hypoxia on cell growth.…”

Proteomics-based investigation of multiple stages of OSCC development indicates that the inhibition of Trx-1 delays oral malignant transformation

“…As a common feature of solid tumors, hypoxia causes oxidative stress and results in a redox imbalance in the tumor microenvironment ( 26 ). Some researchers have reported that the dysfunction and deregulation of hypoxia-related proteins are often an early event during oral carcinogenesis ( 27 , 28 ).…”

Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

“…Hypoxia plays a critical role in oral cancers, pharyngeal cancers, and OPMD [ 118 ]. Cells under conditions of hypoxic stress may present many responses including increased angiogenic capacity, metabolic changes, and modified growth and survival of cells.…”

“…Risk factors (e.g., alcohol, BQ, and cigarette) use may activate the transcription of hypoxia responsive genes. HIF1- α is the major regulator of cellular responses to hypoxia [ 118 ]. The energy metabolism reprogramming and destruction of evading immune are emerging aspects of cancer that are significantly controlled by hypoxia-induced genes that mediate tumor angiogenesis, vascularization, invasion, metastasis, and drug resistance [ 118 , 120 ].…”

“…HIF1- α is the major regulator of cellular responses to hypoxia [ 118 ]. The energy metabolism reprogramming and destruction of evading immune are emerging aspects of cancer that are significantly controlled by hypoxia-induced genes that mediate tumor angiogenesis, vascularization, invasion, metastasis, and drug resistance [ 118 , 120 ]. In light of the multifactorial nature of tumor angiogenesis, reducing hypoxia is one of the possible approaches that could control the progress of oral and pharyngeal cancers.…”