The use of biomarkers in cancer diagnosis, therapy, and prognosis has been highly effective over several decades. Studies of biomarkers in cancer patients pre- and post-treatment and during cancer progression have helped identify cancer stem cells (CSCs) and their related microenvironments. These analyses are critical for the therapeutic application of drugs and the efficient targeting and prevention of cancer progression, as well as the investigation of the mechanism of the cancer development. Biomarkers that characterize CSCs have thus been identified and correlated to diagnosis, therapy, and prognosis. However, CSCs demonstrate elevated levels of plasticity, which alters their functional phenotype and appearance by interacting with their microenvironments, in response to chemotherapy and radiotherapeutics. In turn, these changes induce different metabolic adaptations of CSCs. This article provides a review of the most frequently used CSCs and stem cell markers.

The reprogramming of somatic cells to pluripotent stem cells has immense potential for use in regenerating or redeveloping tissues for transplantation, and the future application of this method is one of the most important research topics in regenerative medicine. These cells are generated from normal cells, adult stem cells, or neoplastic cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, and NANOG, and can differentiate into all tissue types in adults, both in vitro and in vivo. However, tumorigenicity, immunogenicity, and heterogeneity of cell populations may hamper the use of this method in medical therapeutics. The risk of cancer formation is dependent on mutations of these stemness genes during the transformation of pluripotent stem cells to cancer cells and on the alteration of the microenvironments of stem cell niches at genetic and epigenetic levels. Recent reports have shown that the generation of induced pluripotent stem cells (iPSCs) derived from human fibroblasts could be induced using chemicals, which is a safe, easy, and clinical-grade manufacturing strategy for modifying the cell fate of human cells required for regeneration therapies. This strategy is one of the future routes for the clinical application of reprogramming therapy. Therefore, this review highlights the recent progress in research focused on decreasing the tumorigenic risk of iPSCs or iPSC-derived organoids and increasing the safety of iPSC cell preparation and their application for therapeutic benefits.

Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21^CIP1. The loss of the frizzed receptor 7 and the gain of p21^CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.

There is considerable cellular diversity in the human stomach, which has helped to clarify cell plasticity in normal development and tumorigenesis. Thus, the stomach is an interesting model for understanding cellular plasticity and for developing prospective anticancer therapeutic agents. However, many questions remain regarding the development of cancers in vivo and in vitro in two- or three-dimensional (2D/3D) cultures, as well as the role of Helicobacter pylori (H. p.) infection. Here, we focus on the characteristics of cancer stem cells and their derived 3D organoids in culture, including the formation of stem cell niches. We define the conditions required for such organoid culture in vitro and examine the ability of such models for testing the use of anticancer agents. We also summarize the signaling cascades and the specific markers of stomach-cancer-derived organoids induced by H. p. infection, and their stem cell niches.

Stomach cancer has a high mortality, which is partially caused by an absence of suitable biomarkers to allow detection of the initiation stages of cancer progression. Thus, identification of critical biomarkers associated with gastric cancer (GC) is required to advance its clinical diagnoses and treatment. Recent studies using tracing models for lineage analysis of GC stem cells indicate that the cell fate decision of the gastric stem cells might be an important issue for stem cell plasticity. They include leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5⁺), Cholecystokinin receptor 2 (Cckr2⁺), and axis inhibition protein 2 (Axin2⁺) as the stem cell markers in the antrum, Trefoil Factor 2 (TFF2⁺), Mist1⁺ stem cells, and Troy+ chief cells in the corpus. By contrast, Estrogen receptor 1 (eR1), Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), SRY (sex determining region Y)-box 2 (Sox2), and B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) are rich in both the antrum and corpus regions. These markers might help to identify the cell-lineage identity and analyze the plasticity of each stem cell population. Thus, identification of marker genes for the development of GC and its environment is critical for the clinical application of cancer stem cells in the prevention of stomach cancers.

The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore, new therapeutic strategies targeting tumor suppressor gene products may help prevent the progression of pancreatic cancer. In this review, we discuss several recent clinical trials of pancreatic cancer and recent studies reporting safe and effective treatment modalities for patients with advanced pancreatic cancer.