ABSTRACT

Biological sciences have advanced their dimensions in disease diagnosis over the years. One of the greatest leaps has been the development of in vitro models. In vitro models are beneficial for the study of the progression of various biological systems. With this method, investigators attempt to artificially create microenvironments resembling biological conditions to analyze the biophysical, biochemical, and various other aspects of the concerned systems. Our pivotal concern is the study of cancer cell progression. The somatic cells of living organisms divide and proliferate through the process of mitotic cell division. Malfunctioning of the G0 phase renders the cell cycle checkpoints ineffective, thereby disabling their ability to arrest abnormal cells, which ultimately leads to “cancer”. Cancer is characterized by the rapid and uncontrolled growth of damaged cells, which is often propelled by mutagens such as UV rays, gamma rays, and several other carcinogenic elements. In vitro cancer models utilize cancer stems cells (CSCs) that exhibit properties of stem cells such as pluripotency, self-renewal, and fewer nutrient requirements. The first two properties enable CSCs to regenerate malignant tissues to thus make the tumor resistant to cancer therapies. Primarily, 2D cultures are preferred by most researchers (> 66%) over the inexperience and high expense of 3D models. However, despite the drawbacks, 3D models are recognized and favored by more than 80% of researchers due to their accuracy in capturing the in vivo environment. However, problems such as the high probability of false-positive results might arise while artificially establishing in vivo tumor microenvironments. The development of in vitro models is initiated by the isolation and culturing of CSCs from cancer-positive patients, followed by an analysis of the impacts of various anti-cancer drugs (ACDs) via drug screening. The screening analysis includes checking (a) the rate of chemokine secretion (which attracts immune cells via chemotaxis, thereby resulting in cell death); (b) drug-induced angiogenesis; (c) extravasation; (d) cytotoxicity; (e) dormancy of the tumor cell; and (f) negative feedback, if any. Examples of existing in vitro models with the aforesaid properties are Transwell-based models; Spheroid-based models; Tumor-microvessel models, etc. We provide a detailed interpretation of the various aspects and highlight the key findings of the mentioned in vitro models of cancer progression.