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 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 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 Defining lung cancer stem cells exosomal payload of miRNAs in clinical perspective

2020 ◽  
Vol 12 (6) ◽  
pp. 406-421
Author(s):  
Beatrice Aramini ◽  
Valentina Masciale ◽  
Khawaja Husnain Haider
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Clinical Perspective ◽  
Lung Cancer Stem Cells
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