Abstract
Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.
Highlights
Worldwide, lung cancer remains the most commonly diagnosed cancer and the greatest cause of cancer-related death
Oxygen deprivation observed among other respiratory diseases such as severe obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may play a role in the initiation and progression of lung cancer [6]
Studies on 2D lung cancer models have been undermined by the fact that they do not accurately recapitulate the heterogeneity and complexity of the tumor microenvironment (TME)
Summary
Lung cancer remains the most commonly diagnosed cancer and the greatest cause of cancer-related death. According to the latest GLOBOCAN 2018 estimates, lung cancer is the most often diagnosed malignancy (2.1 million new cases) with an age-standardized incidence rate of 22.5 per 100,000 person years worldwide in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths) [1]. Nowadays, there are many new approaches for lung cancer therapies, the 5-year survival rate is still as low as 5–15% [3]. Oxygen deprivation observed among other respiratory diseases such as severe obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may play a role in the initiation and progression of lung cancer [6]
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