scholarly journals Behind the Adaptive and Resistance Mechanisms of Cancer Stem Cells to TRAIL

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1062
Author(s):  
Adriana G. Quiroz-Reyes ◽  
Paulina Delgado-Gonzalez ◽  
Jose Francisco Islas ◽  
Juan Luis Delgado Gallegos ◽  
Javier Humberto Martínez Martínez Garza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Invasion Pathways ◽  
Trail Resistance ◽  
Novel Strategy ◽  
Cancer Remission

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. TRAIL has been widely studied as a novel strategy for tumor elimination, as cancer cells overexpress TRAIL death receptors, inducing apoptosis and inhibiting blood vessel formation. However, cancer stem cells (CSCs), which are the main culprits responsible for therapy resistance and cancer remission, can easily develop evasion mechanisms for TRAIL apoptosis. By further modifying their properties, they take advantage of this molecule to improve survival and angiogenesis. The molecular mechanisms that CSCs use for TRAIL resistance and angiogenesis development are not well elucidated. Recent research has shown that proteins and transcription factors from the cell cycle, survival, and invasion pathways are involved. This review summarizes the main mechanism of cell adaption by TRAIL to promote response angiogenic or pro-angiogenic intermediates that facilitate TRAIL resistance regulation and cancer progression by CSCs and novel strategies to induce apoptosis.

scholarly journals Survival of the Fittest: Cancer Stem Cells in Therapeutic Resistance and Angiogenesis

2008 ◽  
Vol 26 (17) ◽  
pp. 2839-2845 ◽  
Author(s):  
Christine E. Eyler ◽  
Jeremy N. Rich
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Therapeutic Resistance ◽  
Antiangiogenic Agents ◽  
Cancer Therapies ◽  
Tumor Initiating Cells

In an increasing number of cancers, tumor populations called cancer stem cells (CSCs), or tumor-initiating cells, have been defined in functional assays of self-renewal and tumor initiation. Moreover, recent work in several different cancers has suggested the CSC population as a source of chemotherapy and radiation-therapy resistance within tumors. Work in glioblastoma and breast cancers supports the idea that CSCs may possess innate resistance mechanisms against radiation- and chemotherapy-induced cancer cell death, allowing them to survive and initiate tumor recurrence. Several resistance mechanisms have been proposed, including amplified checkpoint activation and DNA damage repair as well as increased Wnt/β-catenin and Notch signaling. Novel targeted therapies against the DNA damage checkpoint or stem-cell maintenance pathways may sensitize CSCs to radiation or other therapies. Another important category of cancer therapies are antiangiogenic and vascular targeting agents, which are also becoming integrated in the treatment paradigm of an increasing number of cancers. Recent results from our laboratory and others support a role for CSCs in the angiogenic drive as well as the mechanism of antiangiogenic agents. Identifying and targeting the molecular mechanisms responsible for CSC therapeutic resistance may improve the efficacy of current cancer therapies.

A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms

2015 ◽  
Vol 31 ◽  
pp. 16-27 ◽  
Author(s):  
Monica Cojoc ◽  
Katrin Mäbert ◽  
Michael H. Muders ◽  
Anna Dubrovska
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Therapy Resistance

scholarly journals Targeting Cancer Stem Cells in Triple-Negative Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 965 ◽  
Author(s):  
Park ◽  
Choi ◽  
Nam
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Therapy Resistance ◽  
Therapeutic Effects ◽  
Self Renewal ◽  
The Future

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that lacks targeted therapy options, and patients diagnosed with TNBC have poorer outcomes than patients with other breast cancer subtypes. Emerging evidence suggests that breast cancer stem cells (BCSCs), which have tumor-initiating potential and possess self-renewal capacity, may be responsible for this poor outcome by promoting therapy resistance, metastasis, and recurrence. TNBC cells have been consistently reported to display cancer stem cell (CSC) signatures at functional, molecular, and transcriptional levels. In recent decades, CSC-targeting strategies have shown therapeutic effects on TNBC in multiple preclinical studies, and some of these strategies are currently being evaluated in clinical trials. Therefore, understanding CSC biology in TNBC has the potential to guide the discovery of novel therapeutic agents in the future. In this review, we focus on the self-renewal signaling pathways (SRSPs) that are aberrantly activated in TNBC cells and discuss the specific signaling components that are involved in the tumor-initiating potential of TNBC cells. Additionally, we describe the molecular mechanisms shared by both TNBC cells and CSCs, including metabolic plasticity, which enables TNBC cells to switch between metabolic pathways according to substrate availability to meet the energetic and biosynthetic demands for rapid growth and survival under harsh conditions. We highlight CSCs as potential key regulators driving the aggressiveness of TNBC. Thus, the manipulation of CSCs in TNBC can be a targeted therapeutic strategy for TNBC in the future.

scholarly journals EMT and Stemness—Key Players in Pancreatic Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1136 ◽  
Author(s):  
Eva Rodriguez-Aznar ◽  
Lisa Wiesmüller ◽  
Bruno Sainz ◽  
Patrick C. Hermann
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Developmental Process ◽  
Therapy Resistance ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition

Metastasis and tumor progression are the major cause of death in patients suffering from pancreatic ductal adenocarcinoma. Tumor growth and especially dissemination are typically associated with activation of an epithelial-to-mesenchymal transition (EMT) program. This phenotypic transition from an epithelial to a mesenchymal state promotes migration and survival both during development and in cancer progression. When re-activated in pathological contexts such as cancer, this type of developmental process confers additional stemness properties to specific subsets of cells. Cancer stem cells (CSCs) are a subpopulation of cancer cells with stem-like features that are responsible for the propagation of the tumor as well as therapy resistance and cancer relapse, but also for circulating tumor cell release and metastasis. In support of this concept, EMT transcription factors generate cells with stem cell properties and mediate chemoresistance. However, their role in pancreatic ductal adenocarcinoma metastasis remains controversial. As such, a better characterization of CSC populations will be crucial in future development of therapies targeting these cells. In this review, we will discuss the latest updates on the mechanisms common to pancreas development and CSC-mediated tumor progression.

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 Dietary Phytochemicals Targeting Cancer Stem Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 899 ◽  
Author(s):  
Alena Liskova ◽  
Peter Kubatka ◽  
Marek Samec ◽  
Pavol Zubor ◽  
Milos Mlyncek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Clinical Research ◽  
Cancer Progression ◽  
Fruits And Vegetables ◽  
Therapy Resistance ◽  
Metastasis Formation ◽  
Self Renewal ◽  
Anticancer Effects ◽  
Dietary Phytochemicals

There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, invasiveness, metastasis formation, and therapy resistance. Anticancer effects of phytochemicals are also directed to target CSCs. Here we provide a comprehensive review of dietary phytochemicals targeting CSCs. Moreover, we evaluate and summarize studies dealing with effects of dietary phytochemicals on CSCs of various malignancies in preclinical and clinical research. Dietary phytochemicals have a significant impact on CSCs which may be applied in cancer prevention and treatment. However, anticancer effects of plant derived compounds have not yet been fully investigated in clinical research.

scholarly journals Exosomes and Cancer Stem Cells in Cancer Immunity: Current Reports and Future Directions

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 441
Author(s):  
Na Kyeong Lee ◽  
Vinoth Kumar Kothandan ◽  
Sangeetha Kothandan ◽  
Youngro Byun ◽  
Seung Rim Hwang
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Immunomodulatory Effects ◽  
Future Directions ◽  
Cancer Immunity ◽  
Different Types ◽  
Underlying Mechanisms

Cancer stem cells (CSCs), which have the capacity to self-renew and differentiate into various types of cells, are notorious for their roles in tumor initiation, metastasis, and therapy resistance. Thus, underlying mechanisms for their survival provide key insights into developing effective therapeutic strategies. A more recent focus has been on exosomes that play a role in transmitting information between CSCs and non-CSCs, resulting in activating CSCs for cancer progression and modulating their surrounding microenvironment. The field of CSC-derived exosomes (CSCEXs) for different types of cancer is still under exploration. A deeper understanding and further investigation into CSCEXs’ roles in tumorigenicity and the identification of novel exosomal components are necessary for engineering exosomes for the treatment of cancer. Here, we review the features of CSCEXs, including surface markers, cargo, and biological or physiological functions. Further, reports on the immunomodulatory effects of CSCEXs are summarized, and exosome engineering for CSC-targeting is also discussed.

scholarly journals Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
He-Ming Zhou ◽  
Ji-Gang Zhang ◽  
Xue Zhang ◽  
Qin Li
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Patient Outcomes ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Clinical Perspective ◽  
Differentiation Potential ◽  
Underlying Processes ◽  
Improve Patient

AbstractCancer stem cells (CSCs) show a self-renewal capacity and differentiation potential that contribute to tumor progression and therapy resistance. However, the underlying processes are still unclear. Elucidation of the key hallmarks and resistance mechanisms of CSCs may help improve patient outcomes and reduce relapse by altering therapeutic regimens. Here, we reviewed the identification of CSCs, the intrinsic and extrinsic mechanisms of therapy resistance in CSCs, the signaling pathways of CSCs that mediate treatment failure, and potential CSC-targeting agents in various tumors from the clinical perspective. Targeting the mechanisms and pathways described here might contribute to further drug discovery and therapy.

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