Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting

Abstract

Cancer is characterized by an abnormal growth of the cells in an uncontrolled manner. These cells have the potential to invade and can eventually turn into malignancy, leading to highly fatal forms of tumor. Small subpopulations of cancer cells that are long-lived with the potential of excessive self-renewal and tumor formation are called cancer stem cells (CSCs) or cancer-initiating cells or tumor stem cells. CSCs can be found in tissues, such as breast, brain, lung, liver, ovary, and testis; however, their origin is still a matter of debate. These cells can differentiate and possess self-renewal capacity maintained by numerous intracellular signal transduction pathways, such as the Wnt/β-catenin signaling, Notch signaling, transforming growth factor-β signaling, and Hedgehog signaling. They can also contribute to numerous malignancies and are an important reason for tumor recurrence and metastasis because they are resistant to the known therapeutic strategies that mainly target the bulk of the tumor cells. This review contains collected and compiled information after analyzing published works of the last three decades. The goal was to gather information of recent breakthroughs related to CSCs, strategies to target CSCs’ niche (e.g., nanotechnology with tumor biology), and their signaling pathways for cancer therapy. Moreover, the role of metformin, an antidiabetic drug, acting as a chemotherapeutic agent on CSCs by inhibiting cellular transformation and its selective killing is also addressed.

Activation of the Anaphase Promoting Complex Reverses Multiple Drug Resistant Cancer in a Canine Model of Multiple Drug Resistant Lymphoma

“…However, the relevance of metformin to counteract drug resistant cancer development has not been well studied. In a recent review, the ability of metformin to inhibit the activity of cancer stem cells was considered [ 20 ]. It has been found that metformin can increase the sensitivity of cancer stem cells to chemotherapy through a variety of methods, including improving vascular normalization and suppressing tumor angiogenesis in metastatic breast cancer cells.…”

Development and Optimization of a Prognostic Model Associated with Stemness Genes in Hepatocellular Carcinoma

“…Cancer stem cells (CSCs) are self-renewal cells, which can promote the occurrence and metastasis of tumors and enhance the drug resistance of tumor treatment [4]. Transcriptomebased studies in multiple tumors have revealed a significant link between tumor stemness and patient prognosis and tumor immune microenvironment [5][6][7].…”

“…In recent years, the tumor stemness has attracted much attention. The main characteristics of tumor stemness are the strong self-renewal ability and increased tumor heterogeneity [ 3 – 4 ]. Many studies have shown that tumor stemness plays an important role in tumor metastasis, differentiation, and drug resistance [ 9 , 10 ].…”

Assessing Putative Markers of Colorectal Cancer Stem Cells: From Colonoscopy to Gene Expression Profiling

“…Identifying and understanding CSCs will increase cancer diagnosis methods and enhance early patient stratification, leading to new and more efficient therapies specifically targeting this fraction of tumor cells and the improvement of the overall outcome of CRC patients [ 33 , 34 ]. As a consequence, we combined clinical settings with fundamental research, in order to assess genetic methods of identifying and characterizing CSCs.…”