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Introduction
Cancer is one of the most common causes of premature death, affecting more than 20 million people worldwide [1, 2]. The number of cancer patients is predicted to double over the next 50 years due to population aging [3]. Amidst the search for effective cancer therapy, cancer stem cells (CSCs) have been proposed as a new model of tumor initiation and a potential target for novel treatment. CSCs refer to a subpopulation within the tumor mass that exhibits unique genetic and phenotypic features similar to traditional stem cells. CSCs largely resist conventional chemotherapy, resulting in relapses and metastases [4, 5–6].
Therapeutics targeting CSCs'distinct self-renewal and differentiation capacities expand possibilities for cancer treatment [7, 8]. In the past decades, there has been accumulating evidence demonstrating CSCs'mechanisms [4]. Preclinical studies showing positive results from targeting CSCs’ signaling pathways have pushed forward the clinical translation of CSC-based therapies [9, 10]. Crosstalk between CSCs and the tumor microenvironment (TME), including extracellular matrix and immune cells, is critical to cancer biology [11, 12–13]. Recognizing CSCs’ essential role in cancer development and their pivotal potential for therapeutic development, the establishment of a biological model that recapitulates CSCs and TME will facilitate a better understanding of tumor initiation and progression, while also serving as a screening platform for CSC-based therapies.
In this review article, we explore the potential of the human embryonal carcinoma NTERA-2 clonal cell line, known as NTERA-2 cl.D1 or NT2/D1 [14, 15], which satisfies both CSC and TME properties. Equally important, NT2/D1 cells have been demonstrated to differentiate into non-cancerous cells under proper post-mitotic treatments [16, 17], thereby providing novel insights and treatment strategies to induce cell cycle exit in CSCs. Indeed, compelling evidence indicates that NT2/D1 cells primed to commit towards the neural lineage can be used biological models as well as cell transplantation source for central nervous system (CNS) disorders [18, 19, 20, 21, 22–23]. This review paper addresses two key questions: (1) Do NT2/D1 cells display CSC and TME properties suitable for modeling tumor development? (2) Can NT2/D1 cells be utilized as a screening platform for cancer therapeutics? Moreover, we also review the application of NT2/D1 cells as biological models and treatment screening platforms for diseases beyond cancer, i.e., CNS disorders to fully elucidate the...