scholarly journals New Molecules and Old Drugs as Emerging Approaches to Selectively Target Human Glioblastoma Cancer Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Roberto Würth ◽  
Federica Barbieri ◽  
Tullio Florio
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Multimodal Treatment ◽  
Drug Research ◽  
Primary Brain Tumor ◽  
Preclinical Studies ◽  
Current Standard ◽  
Selective Toxicity ◽  
Prospective Application ◽  
Old Drugs

Despite relevant progress obtained by multimodal treatment, glioblastoma (GBM), the most aggressive primary brain tumor, is still incurable. The most encouraging advancement of GBM drug research derives from the identification of cancer stem cells (CSCs), since these cells appear to represent the determinants of resistance to current standard therapies. The goal of most ongoing studies is to identify drugs able to affect CSCs biology, either inducing selective toxicity or differentiating this tumor cell population into nontumorigenic cells. Moreover, the therapeutic approach for GBM could be improved interfering with chemo- or radioresistance mechanisms, microenvironment signals, and the neoangiogenic process. During the last years, molecular targeted compounds such as sorafenib and old drugs, like metformin, displayed interesting efficacy in preclinical studies towards several tumors, including GBM, preferentially affecting CSC viability. In this review, the latest experimental results, controversies, and prospective application concerning these promising anticancer drugs will be discussed.

scholarly journals Cellular Immunotherapy Targeting Cancer Stem Cells: Preclinical Evidence and Clinical Perspective

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 543
Author(s):  
Chiara Donini ◽  
Ramona Rotolo ◽  
Alessia Proment ◽  
Massimo Aglietta ◽  
Dario Sangiolo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Indirect Evidence ◽  
Cellular Immunotherapy ◽  
Preclinical Studies ◽  
Clinical Perspective ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Relevant Issue ◽  
Selective Elimination

The term “cancer stem cells” (CSCs) commonly refers to a subset of tumor cells endowed with stemness features, potentially involved in chemo-resistance and disease relapses. CSCs may present peculiar immunogenic features influencing their homeostasis within the tumor microenvironment. The susceptibility of CSCs to recognition and targeting by the immune system is a relevant issue and matter of investigation, especially considering the multiple emerging immunotherapy strategies. Adoptive cellular immunotherapies, especially those strategies encompassing the genetic redirection with chimeric antigen receptors (CAR), hold relevant promise in several tumor settings and might in theory provide opportunities for selective elimination of CSC subsets. Initial dedicated preclinical studies are supporting the potential targeting of CSCs by cellular immunotherapies, indirect evidence from clinical studies may be derived and new studies are ongoing. Here we review the main issues related to the putative immunogenicity of CSCs, focusing on and highlighting the existing evidence and opportunities for cellular immunotherapy approaches with T and non-T antitumor lymphocytes.

scholarly journals Stem cells for the treatment of glioblastoma: a 20-year perspective

CNS Oncology ◽  
2021 ◽  
pp. CNS73
Author(s):  
Anda-Alexandra Calinescu ◽  
McKenzie C Kauss ◽  
Zain Sultan ◽  
Wajd N Al-Holou ◽  
Sue K O’Shea
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Beneficial Effect ◽  
Treatment Resistance ◽  
Primary Brain Tumor ◽  
Therapeutic Agents ◽  
Preclinical Studies

Glioblastoma, the deadliest form of primary brain tumor, remains a disease without cure. Treatment resistance is in large part attributed to limitations in the delivery and distribution of therapeutic agents. Over the last 20 years, numerous preclinical studies have demonstrated the feasibility and efficacy of stem cells as antiglioma agents, leading to the development of trials to test these therapies in the clinic. In this review we present and analyze these studies, discuss mechanisms underlying their beneficial effect and highlight experimental progress, limitations and the emergence of promising new therapeutic avenues. We hope to increase awareness of the advantages brought by stem cells for the treatment of glioblastoma and inspire further studies that will lead to accelerated implementation of effective therapies.

A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells

2020 ◽  
Vol 150 ◽  
pp. 253-261 ◽  
Author(s):  
Guillaume Vares ◽  
Vidhula Ahire ◽  
Shigeaki Sunada ◽  
Eun Ho Kim ◽  
Sei Sai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Multimodal Treatment ◽  
Mtor Inhibitor ◽  
High Grade ◽  
Carbon Ions

scholarly journals Targeting Cancer Stem Cells and Metastasis with Epigenetic Modulation and Anti-HER2 Therapy: Phase I/II Trial of Vorinostat in Combination with Lapatinib

2020 ◽  
pp. 1-12
Author(s):  
Saranya Chumsri ◽  
Amanda Schech ◽  
Angela Brodie ◽  
Jane Lewis ◽  
Katherine Tkaczuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Phase I ◽  
Single Agent ◽  
Preclinical Studies ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Purpose: Considerable preclinical and clinical data indicate that only a small subset of tumor cells has longterm proliferating capacity. These cells are termed cancer stem cells (CSCs). Failure to eradicate CSCs is hypothesized to be a cause of cancer recurrence after potentially curative therapies. Therefore, approaches that target CSCs have the potential to improve outcomes. We evaluated the combination of vorinostat and lapatinib to target CSCs and metastasis. Experimental Design: We conducted preclinical studies and a phase I/II clinical trial to determine the effects of vorinostat and lapatinib to CSCs. Results: Our preclinical studies demonstrated that vorinostat and lapatinib further reduced CSCs compared to either single agent. Reduction in self-renewal proteins, mammospheres, epithelial-mesenchymal transition (EMT) markers, and cell migration was also observed. Based on these findings, the combination was evaluated in the phase I trial to which a total of 12 patients were enrolled. Dose-limiting toxicity was not observed in phase I, and the recommended phase II dose was vorinostat 400 mg 4 days on 3 days off and lapatinib 1,250 mg daily. In HER2-positive breast cancer patients, the clinical benefit rate was observed in 43% of subjects. Interestingly, patients who remained on vorinostat and lapatinib did not develop any new site of metastasis. Conclusion: The combination of vorinostat and lapatinib is safe and active in HER2-positive breast cancer. Further studies are needed to evaluate this strategy to target CSCs and metastasis.

scholarly journals Wnt-signaling pathway in pathogenesis of glioblastoma multiforme

2019 ◽  
Vol 5 (4) ◽  
pp. 94-103
Author(s):  
Yu. D. Vasilets ◽  
N. E. Arnotskaya ◽  
I. A. Kudryavtsev ◽  
V. E. Shevchenko
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Biological Processes ◽  
Current Standard ◽  
Immune Resistance ◽  
Oncogenic Driver ◽  
And Migration

The Wnt-signaling pathway regulates various biological processes, such as embryonic development, self-renewal, proliferation, differentiation and migration of stem cells. The Wnt-signaling is involved in tumor progression by aberrant activation in stem-like cells, called cancer stem cells, in different kinds of tumor, including multiform glioblastoma. The Wnt-signaling promotes stemness, invasion, metastasis, therapeutic and immune resistance of cancer stem cells in multiform glioblastoma. To summarize, targeting the Wnt-signaling pathway as an oncogenic driver is the future hope for effective therapy of glioblastoma for which current standard therapy is not effective.In this review, we focused on functions of the Wnt-signaling in cancer stem cells and involvement of the Wnt-signaling pathway in gliomagenesis.

scholarly journals Targeting glioblastoma cancer stem cells: the next great hope?

2014 ◽  
Vol 37 (6) ◽  
pp. E7 ◽  
Author(s):  
Imad Saeed Khan ◽  
Moneeb Ehtesham
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Specific Immunotherapy ◽  
Primary Brain Tumor ◽  
Self Renewal ◽  
Great Hope ◽  
Small Cohort ◽  
Therapy Strategies ◽  
Very High

Glioblastoma multiforme (GBM) is the most common primary brain tumor and is notorious for its poor prognosis. The highly invasive nature of GBM and its inherent resistance to therapy lead to very high rates of recurrence. Recently, a small cohort of tumor cells, called cancer stem cells (CSCs), has been recognized as a subset of tumor cells with self-renewal ability and multilineage capacity. These properties, along with the remarkable tumorigenicity of CSCs, are thought to account for the high rates of tumor recurrence after treatment. Recent research has been geared toward understanding the unique biological characteristics of CSCs to enable development of targeted therapy. Strategies include inhibition of CSC-specific pathways and receptors; agents that increase sensitivity of CSCs to chemotherapy and radiotherapy; CSC differentiation agents; and CSC-specific immunotherapy, virotherapy, and gene therapy. These approaches could inform the development of newer therapeutics for GBM.

scholarly journals Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66371 ◽  
Author(s):  
Patrick C. Hermann ◽  
Sara M. Trabulo ◽  
Bruno Sainz ◽  
Anamaria Balic ◽  
Elena Garcia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Multimodal Treatment ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Term Survival ◽  
Long Term Survival

Identification of Pancreatic Cancer Stem Cells and Selective Toxicity of Chemotherapeutic Agents

2012 ◽  
Vol 143 (1) ◽  
pp. 234-245.e7 ◽  
Author(s):  
Rama Adikrisna ◽  
Shinji Tanaka ◽  
Shunsuke Muramatsu ◽  
Arihiro Aihara ◽  
Daisuke Ban ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Chemotherapeutic Agents ◽  
Selective Toxicity ◽  
Pancreatic Cancer Stem Cells
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