scholarly journals Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets

2020 ◽  
Vol 73 (5) ◽  
pp. 243-249 ◽  
Author(s):  
Hisham F Bahmad ◽  
Robert J Poppiti
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Biology ◽  
Cancer Recurrence ◽  
Chemotherapeutic Agents ◽  
Molecular Signatures ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Successful Management ◽  
The Past

Medulloblastoma (MB) is the most common malignant primary intracranial neoplasm diagnosed in childhood. Although numerous efforts have been made during the past few years to exploit novel targeted therapies for this aggressive neoplasm, there still exist substantial hitches hindering successful management of MB. Lately, progress in cancer biology has shown evidence that a subpopulation of cells within the tumour, namely cancer stem cells (CSCs), are thought to be responsible for the resistance to most chemotherapeutic agents and radiation therapy, accounting for cancer recurrence. Hence, it is crucial to identify the molecular signatures and genetic aberrations that characterise those CSCs and develop therapies that specifically target them. In this review, we aim to give an overview of the main genetic and molecular cues that depict MB-CSCs and provide a synopsis of the novel therapeutic approaches that specifically target this population of cells to attain enhanced antitumorous effects and therefore overcome resistance to therapy.

Role of Organ Specific Cancer Stem Cells in Organ Specific Cancer Progression

2020 ◽  
Vol 6 (2) ◽  
pp. 21
Author(s):  
Muhammad Ali ◽  
Fatima Ali ◽  
Nadia Wajid
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Cancer Therapeutics ◽  
Therapeutic Approaches ◽  
Specific Cancer ◽  
Organ Specific

Since the cancer stem cells (CSC) have been identified in 1997 by Bonnet and Dick, more than 100,000 papers have been published on the CSC. Huge research on cancer stem cells helped the scientists to rethink about the cancer therapeutics as classic way of chemotherapy is ineffective because chemotherapy failed to kill these cells, the only reason of cancer relapse. The cancer theory of stem cells is one of the most trending theory in stem cells and cancer biology focusing on the understanding of biology of cancer cells for an enhanced and improved therapeutic approaches should be applied to cure the cancer. This mini-review is a short overview on the role of organ specific cancer stem cells in the organ specific cancer progression.

scholarly journals The Evolving Landscape of Cancer Stem Cells and Ways to Overcome Cancer Heterogeneity

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 532 ◽  
Author(s):  
Hiroaki Taniguchi ◽  
Yasunori Suzuki ◽  
Yukikazu Natori
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Biology ◽  
Signaling Cascades ◽  
Cancer Stemness ◽  
Signaling Systems ◽  
Cancer Heterogeneity ◽  
The Past ◽  
Suitable Target ◽  
Target Molecules

Cancer stem cells (CSCs) with therapeutic resistance and plasticity can be found in various types of tumors and are recognized as attractive targets for treatments. As CSCs are derived from tissue stem or progenitor cells, and/or dedifferentiated mature cells, their signal transduction pathways are critical in the regulation of CSCs; chronic inflammation causes the accumulation of genetic mutations and aberrant epigenetic changes in these cells, potentially leading to the production of CSCs. However, the nature of CSCs appears to be stronger than the treatments of the past. To improve the treatments targeting CSCs, it is important to inhibit several molecules on the signaling cascades in CSCs simultaneously, and to overcome cancer heterogeneity caused by the plasticity. To select suitable target molecules for CSCs, we have to explore the landscape of CSCs from the perspective of cancer stemness and signaling systems, based on the curated databases of cancer-related genes. We have been studying the integration of a broad range of knowledge and experiences from cancer biology, and also from other interdisciplinary basic sciences. In this review, we have introduced the concept of developing novel strategies targeting CSCs.

scholarly journals Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Qinglei Zhan ◽  
Chunmei Wang ◽  
Saiming Ngai
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Recurrence ◽  
Basic Research ◽  
Ovarian Cancer Cells ◽  
Therapeutic Approaches ◽  
Ovarian Cancer Stem Cells ◽  
Cancer Disease ◽  
Effective Strategies

Ovarian cancer is a highly lethal disease among all gynecologic malignancies and is the fifth leading cause of cancer-related death in women. Although the standard combination of surgery and chemotherapy was initially effective in patients with ovarian cancer, disease relapse commonly occurred due to the generation of chemoresistance. It has been reported that cancer stem cells (CSCs) are involved in drug resistance and cancer recurrence. Over the past decades, increasing studies have been done to identify CSCs from human ovarian cancer cells. The present paper will summarize different investigations on ovarian CSCs, including isolation, mechanisms of chemoresistance, and therapeutic approaches. Although there are still numerous challenges to translate basic research to clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent ovarian cancer and its recurrence.

Approaches for the synthesis, chemical modification and biological properties of N-acylphenothiazines

2021 ◽  
Vol 10 (4) ◽  
pp. 377-392 ◽  
Author(s):  
Iryna Myrko ◽  
Taras Chaban ◽  
Yulia Matiichuk ◽  
Mohammad Arshad ◽  
Vasyl Matiychuk
Keyword(s):  
Experimental Data ◽  
Chemical Modification ◽  
Medicinal Chemistry ◽  
Biological Properties ◽  
Chemotherapeutic Agents ◽  
Present Review ◽  
The Novel ◽  
Pharmacological Activities ◽  
The Past ◽  
Biological Potential

In this review we systematized the theoretical and experimental data concerning the versatile approaches for the synthesis of N-acylphenothiazines. The aim of the study was to compile the literature reported worldwide in the past 20 years. This article also reviewed the analysis of pharmacological activities of these heterocycles as one of the promising chemotherapeutic objects for the modern bioorganic and medicinal chemistry. It has been hypothesized that the enormous biological potential of these moieties is due to the radical nature in the acyl moiety. Therefore, the present review will be a good contribution to the literature and will provide the platform for the medicinal chemistry researchers to carry out more studies aiming the N-acylphenothiazine moieties as the novel chemotherapeutic agents.

scholarly journals Mitotic quiescence in hepatic cancer stem cells: An incognito mode

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Kandasamy Ashokachakkaravarthy ◽  
Biju Pottakkat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Tumor Formation ◽  
Proliferating Cells ◽  
Recurrence Rates

Hepatocellular carcinoma represents one of the most aggressive cancers with high recurrence rates. The high recurrence is a major problem in the management of this disease. Cancer stem cells (CSCs) are often regarded as the basis of cancer recurrence. The anti-proliferative therapy kills the proliferating cells but induces mitotic quiescence in CSCs which remain as residual dormant CSCs. Later on, withdrawal of treatment reactivates the residual CSCs from dormancy to produce new cancer cells. The proliferation of these newly formed cancer cells initiates new tumor formation in the liver leading to tumor recurrence. HCC cells evade the immune surveillance via modulating the key immune cells by alpha feto-protein (AFP) secreted from CSCs or hepatic progenitor cells. This AFP mediated immune evasion assists in establishing new tumors by cancer cells in the liver. In this review, we will summarise the CSC mechanisms of recurrence, mitotic quiescence, dormancy and reactivation of CSCs, metastasis and immune evasion of hepatocellular carcinoma.

scholarly journals Whole Organism Model to Study Molecular Mechanisms of Differentiation and Dedifferentiation

Biology ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 79
Author(s):  
Areeba Anwar ◽  
Ruqaiyyah Siddiqui ◽  
Naveed Ahmed Khan
Keyword(s):  
Stem Cells ◽  
Cellular Differentiation ◽  
Molecular Mechanisms ◽  
Cancer Recurrence ◽  
Acanthamoeba Castellanii ◽  
Phenotypic Switching ◽  
Therapeutic Approaches ◽  
Unicellular Organism ◽  
Organism Model ◽  
Differentiation And Dedifferentiation

Cancer recurrence has remained a significant challenge, despite advances in therapeutic approaches. In part, this is due to our incomplete understanding of the biology of cancer stem cells and the underlying molecular mechanisms. The phenomenon of differentiation and dedifferentiation (phenotypic switching) is not only unique to stem cells but it is also observed in several other organisms, as well as evolutionary-related microbes. Here, we propose the use of a primitive eukaryotic unicellular organism, Acanthamoeba castellanii, as a model to study the molecular mechanisms of cellular differentiation and dedifferentiation.

scholarly journals The Effects of TGF-β Signaling on Cancer Cells and Cancer Stem Cells in the Bone Microenvironment

2019 ◽  
Vol 20 (20) ◽  
pp. 5117 ◽  
Author(s):  
Mitsuru Futakuchi ◽  
Kris Lami ◽  
Yuri Tachibana ◽  
Yukari Yamamoto ◽  
Masahiro Furukawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Skin Flap ◽  
Chemotherapeutic Agents ◽  
Bmp Signaling ◽  
Bone Microenvironment

Background: Transforming growth factor-β (TGF-β) plays a key role in bone metastasis formation; we hypothesized the possible involvement of TGF-β in the induction of cancer stem cells (CSCs) in the bone microenvironment (micro-E), which may be responsible for chemo-resistance. Methods: Mouse mammary tumor cells were implanted under the dorsal skin flap over the calvaria and into a subcutaneous (subQ) lesions in female mice, generating tumors in the bone and subQ micro-Es. After implantation of the tumor cells, mice were treated with a TGF-β R1 kinase inhibitor (R1-Ki). Results: Treatment with R1-Ki decreased tumor volume and cell proliferation in the bone micro-E, but not in the subQ micro-E. R1-Ki treatment did not affect the induction of necrosis or apoptosis in either bone or subQ micro-E. The number of cells positive for the CSC markers, SOX2, and CD166 in the bone micro-E, were significantly higher than those in the subQ micro-E. R1-Ki treatment significantly decreased the number of CSC marker positive cells in the bone micro-E but not in the subQ micro-E. TGF-β activation of the MAPK/ERK and AKT pathways was the underlying mechanism of cell proliferation in the bone micro-E. BMP signaling did not play a role in cell proliferation in either micro-E. Conclusion: Our results indicated that the bone micro-E is a key niche for CSC generation, and TGF-β signaling has important roles in generating CSCs and tumor cell proliferation in the bone micro-E. Therefore, it is critically important to evaluate responses to chemotherapeutic agents on both cancer stem cells and proliferating tumor cells in different tumor microenvironments in vivo.

scholarly journals Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1450 ◽  
Author(s):  
Patrick Santos ◽  
Fausto Almeida
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapy Resistance ◽  
Chemotherapeutic Agents ◽  
Exosomal Mirnas ◽  
Key Factor

Tumor microenvironment (TME) is composed of different cellular populations, such as stromal, immune, endothelial, and cancer stem cells. TME represents a key factor for tumor heterogeneity maintenance, tumor progression, and drug resistance. The transport of molecules via extracellular vesicles emerged as a key messenger in intercellular communication in the TME. Exosomes are small double-layered lipid extracellular vesicles that can carry a variety of molecules, including proteins, lipids, and nucleic acids. Exosomal miRNA released by cancer cells can mediate phenotypical changes in the cells of TME to promote tumor growth and therapy resistance, for example, fibroblast- and macrophages-induced differentiation. Cancer stem cells can transfer and enhance drug resistance in neighboring sensitive cancer cells by releasing exosomal miRNAs that target antiapoptotic and immune-suppressive pathways. Exosomes induce drug resistance by carrying ABC transporters, which export chemotherapeutic agents out of the recipient cells, thereby reducing the drug concentration to suboptimal levels. Exosome biogenesis inhibitors represent a promising adjunct therapeutic approach in cancer therapy to avoid the acquisition of a resistant phenotype. In conclusion, exosomal miRNAs play a crucial role in the TME to confer drug resistance and survivability to tumor cells, and we also highlight the need for further investigations in this promising field.

CanStem111P trial: A phase III study of napabucasin (BBI-608) plus nab-paclitaxel (nab-PTX) with gemcitabine (gem) in adult patients with metastatic pancreatic adenocarcinoma (mPDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4148-TPS4148 ◽  
Author(s):  
Tanios S. Bekaii-Saab ◽  
Chung-Pin Li ◽  
Takuji Okusaka ◽  
Bert H. O'Neil ◽  
Michele Reni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Disease Control ◽  
Performance Status ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Study Population

TPS4148 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinical studies suggest that napabucasin sensitizes heterogeneous cancer cells to chemotherapeutic agents, including nab-PTX and gem. Encouraging anticancer activity in mPDAC was observed in a phase Ib (El-Rayes et al, ASCO 2016) study of 37 pts, reporting 93% (28/30) disease control rate (DCR) and 50% (15/30) overall response rate (ORR), with 1 complete and 14 partial responses and prolonged disease control ( > 24 wks) in 57% (17/30) of pts who have had a RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia and Asia. Methods: This study (ClinicalTrials.gov NCT02993731) will assess the efficacy of napabucasin+nab-PTX+gem vs nab-PTX+gem in pts with mPDAC (n = 1132). Pts must have been diagnosed with mPDAC < 6 weeks prior to randomization and not have received treatment for metastatic disease. Pts are randomized in a 1:1 ratio to receive napabucasin 240 mg PO twice daily continuously plus nab-PTX+gem IV weekly for 3 out every 4 weeks, or nab-PTX+gem IV weekly for 3 out every 4 weeks. Pts will be stratified by geography, performance status and presence of liver metastases. Treatment will continue until disease progression, death, intolerability or patient/investigator decision to stop. Primary endpoint is overall survival (OS) in the general study population (HR 0.80 for OS improvement from 8.5 to 10.63 months); secondary endpoints include progression free survival (PFS), OS and PFS in the biomarker positive sub-population, ORR and DCR, safety and quality of life. In addition, blood and tumor archival tissue will be assessed for pharmacokinetic and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02993731.

scholarly journals Therapeutic Approaches to Target Cancer Stem Cells

Cancers ◽  
2011 ◽  
Vol 3 (3) ◽  
pp. 3331-3352 ◽  
Author(s):  
Arlhee Diaz ◽  
Kalet Leon
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Approaches ◽  
Target Cancer
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