Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Abstract

Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor–tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

Recent advances in 3D bioprinted tumor models for personalized medicine

“…Up to now, 11 genetically differentiated and two main histopathological subtypes of this cancer type were classified. Small-cell lung cancer, referring to 15% of cases, is the most aggressive type in the metastatic stage [48] . One of the reasons for the high mortality rate is late diagnosis.…”

Patient-Derived Lung Cancer “Sandwich Cultures” with a Preserved Tumor Microenvironment

“…1 In lung cancer research, patient-derived three-dimensional (3D) in vitro tissue models are promising tools for translational research as well as personalized medicine. 2 Different concepts have been introduced to emulate the NSCLC tumor niche in vitro , such as spheroids, or scaffold-based and microfluidic models. 3–6 These models recapitulated the cytological features and markers of lung cancer, and demonstrated the utility of drug screening and separation of cancer cells from liquid biopsy.…”

Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells

“…Therefore, to understand the molecular mechanisms responsible for the spatially growing EMT changes in RPE cells, it becomes necessary to study the effects of both TGF-β2 and hypoxia, as possible major pathogenic inducers using a reliable 3D cell culture system that replicates such a spatial environment. In fact, in addition to the conventional 2D cell cultures, such an in vitro 3D spheroid model has been identified as a powerful tool for studying the molecular mechanisms of EMT as well as hypoxia within cancerous cells [ 25 , 26 , 27 , 28 ].…”