Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Abstract

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

“…CSCs attain excessive levels of self-renewal through participation in stemness pathways, including Hedgehog [79][80][81][82], Notch [83][84][85][86][87], Wnt/β-catenin [83,88,89], Nanog [90][91][92], NF-kB [93,94], RAS [95,96], p38 MAPK [97][98][99][100], PI3K [100][101][102], and EGFR pathways [103][104][105]. As has been elaborated, CSC participation in these pathways is key to its differentiative capacity and overexpressed stem pathways can be associated with biomass growth in tumors [58,106,107].…”

Metastasis and MAPK Pathways

“…Despite the fact that the presence of cancer stem cells (CSCs) is still widely debated, the CSC hypothesis is of significant clinical significance, because it has the potential to explain tumor resistance to chemotherapy, cancer progression, and recurrence in cancer patients [ 72 , 73 ]. CSCs or tumor-initiating cells (TICs) represent a sub-population of cells that exhibit self-renewal ability and the capacity to differentiate.…”

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments

“…These have been proposed to be the causes of cancer progression, metastasis and drug resistance [12]. Recently the scientific community has discussed specific aspects of these cancer related actors, considering them as one of the most interesting and unknown causes of tumor dissemination [13,14]. In particular, they seem to be present in both early and locally advanced stages, as shown by Masciale et al for adenocarcinoma and squamous cell carcinoma of the lungs [15].…”