scholarly journals Drug resistance and Cancer stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuan Li ◽  
Zhenning Wang ◽  
Jaffer A. Ajani ◽  
Shumei Song
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Abc Transporters ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Drug Efflux ◽  
Extrinsic Factors ◽  
Mesenchymal Transition ◽  
Damage Response ◽  
Therapeutic Compounds

AbstractTherapy resistance is a major problem when treating cancer patients as cancer cells develop mechanisms that counteract the effect of therapeutic compounds, leading to fit and more aggressive clones that contribute to poor prognosis. Therapy resistance can be both intrinsic and/or acquired. These are multifactorial events, and some are related to factors including adaptations in cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), deregulation of key signaling pathways, drug efflux through ABC transporters, acquired mutations, evading apoptosis, and activation of DNA damage response among others. Among these factors, CSCs represent the major source of therapy resistance. CSCs are a subset of tumor cells that are capable of self-renewal and multilineage progenitor expansion that are known to be intrinsically resistant to anticancer treatments. Multiple clones of CSCs pre-exist, and some can adopt and expand easily to changes in the tumor microenvironment (TME) and/or in response to radio- and chemotherapy. A combination of both intrinsic and extrinsic factors contributes to CSC-mediated therapy resistance. In this review, we will focus on CSCs and therapy resistance as well as suggest strategies to eliminate CSCs and, therefore, overcome resistance.

scholarly journals Different Shades of L1CAM in the Pathophysiology of Cancer Stem Cells

2020 ◽  
Vol 9 (5) ◽  
pp. 1502 ◽  
Author(s):  
Marco Giordano ◽  
Ugo Cavallaro
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Biological Properties ◽  
Cytotoxic Agents ◽  
Tumor Initiating Cells ◽  
Mesenchymal Transition ◽  
Tumor Types

L1 cell adhesion molecule (L1CAM) is aberrantly expressed in several tumor types where it is causally linked to malignancy and therapy resistance, acting also as a poor prognosis factor. Accordingly, several approaches have been developed to interfere with L1CAM function or to deliver cytotoxic agents to L1CAM-expressing tumors. Metastatic dissemination, tumor relapse and drug resistance can be fueled by a subpopulation of neoplastic cells endowed with peculiar biological properties that include self-renewal, efficient DNA repair, drug efflux machineries, quiescence, and immune evasion. These cells, known as cancer stem cells (CSC) or tumor-initiating cells, represent, therefore, an ideal target for tumor eradication. However, the molecular and functional traits of CSC have been unveiled only to a limited extent. In this context, it appears that L1CAM is expressed in the CSC compartment of certain tumors, where it plays a causal role in stemness itself and/or in biological processes intimately associated with CSC (e.g., epithelial-mesenchymal transition (EMT) and chemoresistance). This review summarizes the role of L1CAM in cancer focusing on its functional contribution to CSC pathophysiology. We also discuss the clinical usefulness of therapeutic strategies aimed at targeting L1CAM in the context of anti-CSC treatments.

scholarly journals Cancer Stem Cells in Intrahepatic Cholangiocarcinoma; Their Molecular Basis, and Therapeutic Implications

2022 ◽  
Vol 12 ◽  
Author(s):  
Keiichi Tamai ◽  
Haruna Fujimori ◽  
Mai Mochizuki ◽  
Kennichi Satoh
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Intrahepatic Cholangiocarcinoma ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Target Therapy ◽  
Therapy Resistance ◽  
Future Perspective ◽  
Cancer Tissue ◽  
Mesenchymal Transition

Cancer tissue consists of heterogenous cell types, and cancer stem cells (CSCs) are a subpopulation of the tissue which possess therapy resistance, tumor reconstruction capability, and are responsible for metastasis. Intrahepatic cholangiocarcinoma (iCCA) is one of the most common type of liver cancer that is highly aggressive with poor prognosis. Since no target therapy is efficient in improving patient outcomes, new therapeutic approaches need to be developed. CSC is thought to be a promising therapeutic target because of its resistance to therapy. Accumulating evidences suggests that there are many factors (surface marker, stemness-related genes, etc.) and mechanisms (epithelial-mesenchymal transition, mitochondria activity, etc.) which are linked to CSC-like phenotypes. Nevertheless, limited studies are reported about the application of therapy using these mechanisms, suggesting that more precise understandings are still needed. In this review, we overview the molecular mechanisms which modulate CSC-like phenotypes, and discuss the future perspective for targeting CSC in iCCA.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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