Targeting Cancer Stem Cells Pathways for the Effective Treatment of Cancer

2020 ◽  
Vol 21 (3) ◽  
pp. 258-278 ◽  
Author(s):  
Ashish Ranjan Dwivedi ◽  
Amandeep Thakur ◽  
Vijay Kumar ◽  
Ira Skvortsova ◽  
Vinod Kumar
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Effective Treatment ◽  
Single Agent ◽  
Clinical Results ◽  
Review Article ◽  
Therapeutic Approaches ◽  
Design Synthesis ◽  
Complete Eradication ◽  
Current Review

Resistance to chemotherapy and relapse are major hurdles for the effective treatment of cancer. Major reason for this is a small sub population of cancer stem cells (CSCs) and its microenvironment. CSCs are critical driving force for several types of cancer, such as gastric, colon, breast and many more. Hence, for the complete eradication of cancer, it is necessary to develop therapeutic approaches that can specifically target CSCs. Chemical agents that target different proteins involved in CSC signaling pathways, either as single agent or simultaneously targeting two or more proteins have generated promising pre-clinical and clinical results. In the current review article, we have discussed various targets and cellular pathways that can be explored for the effective and complete eradication of CSCs. Some latest developments in the field of design, synthesis and screening of ligands to target cancer stem cells have been summarized in the current review article.

scholarly journals Stem Cell Concept in Thyroid Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Cihan Zamur ◽  
Uğur Topal ◽  
Harun Özdemir ◽  
Serdar Altınay
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Thyroid Cancer ◽  
Thyroid Gland ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Clinical Results ◽  
Cell Populations ◽  
Cellular Origin ◽  
Rare Cells

The most frequently diagnosed endocrine cancer, which causes more deaths than any other endocrine cancer, is thyroid cancer. Cancer stem cells are rare cells found in tumors that can regenerate themselves, phenotypically leads to various tumor cell populations and trigger tumorigenesis. Cancer stem cells have been identified in many cancers, including thyroid cancer. Having an understanding of the molecular mechanisms which control the biology of cancer stem cells and the disease processes will help us in designing more rational targeted therapies for aggressive thyroid cancers. In this review, we aimed to present the current accepted knowledge about thyroid stem cells, information regarding the cellular origin of thyroid cancer stem cells, and the clinical results of cancer stem cells present in the thyroid gland.

scholarly journals Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets

Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 7 ◽  
Author(s):  
Lingfeng Fu ◽  
Luke Bu ◽  
Tadahito Yasuda ◽  
Mayu Koiwa ◽  
Takahiko Akiyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Chemotherapy Resistance ◽  
Immune Microenvironment ◽  
Self Renewal ◽  
Current Review ◽  
Gastric Cancer Stem Cells ◽  
Novel Therapeutic Strategies ◽  
The Relationship

Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) are known to be involved in chemotherapy resistance and the development of metastases. Although CSCs harbor self-renewal and tumorigenic abilities, the immune microenvironment surrounding CSCs provides various factors and supports the maintenance of CSC properties. The current review summarizes the accumulating findings regarding the relationship between the immune microenvironment and gastric CSCs (GCSCs), which will support the possibility of developing novel therapeutic strategies for targeting GCSCs.

Activity and tolerability of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk, as a single agent in patients with advanced hematologic malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7029-7029 ◽  
Author(s):  
Arthur E. Frankel ◽  
Marina Konopleva ◽  
Donna Hogge ◽  
David Rizzieri ◽  
Christopher Brooks ◽  
...  
Keyword(s):  
Stem Cells ◽  
Targeted Therapy ◽  
Cancer Stem Cells ◽  
Single Agent ◽  
Hematologic Malignancies ◽  
Single Cycle ◽  
Long Term Outcome ◽  
Interleukin 3 ◽  
Wide Range ◽  
Refractory Aml

7029^ Background: SL-401 is a novel biologic targeted therapy directed to the interleukin-3 receptor (IL-3R). IL-3R is overexpressed on cancer stem cells (CSCs) and tumor bulk relative to normal hematopoietic cells in a wide range of hematologic malignancies including AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Since SL-401 targets both leukemia blasts and CSCs, tumor regression and improvement in long-term outcome is expected. The clinical activity and side effect profile of SL-401 were evaluated in a multicenter Phase I/II trial of patients with advanced hematologic cancers. Methods: Eighty-one patients with advanced hematologic cancers, including relapsed or refractory AML (n = 59) and heavily pretreated BPDCN (n = 4), have been enrolled. Patients received a single cycle of SL-401 via 15-minute IV infusion to determine the maximum tolerated dose (MTD) and assess antitumor activity. Results: A single cycle of SL-401 demonstrated single agent activity in relapsed or refractory AML patients, including 2 durable CRs of 8 and 25+ months duration and multiple cases of blast reductions. SL-401, when delivered at therapeutically relevant doses, was associated with > 3-fold greater median overall survival (OS) in AML patients who received 2+ prior lines of treatment relative to historical results. In addition, 3 heavily pre-treated patients with BPDCN, an uncommon malignancy that expresses high levels of IL-3R and is ultrasensitive to SL-401 (IC50 values in the femtomolar [10-15 M] range), had CRs, with durations of 5, 3+ and 1+ months. The MTD was 16.6 µg/kg/day; the dose-limiting toxicities of hypoalbuminemia and edema, which are manifestations of capillary leak, occurred at 22.1 µg/kg/day. Other ≥ Grade 3 adverse events included transient transaminase elevations. There was no treatment-related myelosuppression. Conclusions: SL-401 was well tolerated and demonstrated single agent activity in patients with relapsed or refractory AML and BPDCN. Based on these findings, single agent SL-401 given in multiple cycles will be advanced into pivotal studies of AML (3rd-line) and BPDCN. Clinical trial information: NCT00397579.

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

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 Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2598
Author(s):  
Mieun Lee-Theilen ◽  
Julia R. Hadhoud ◽  
Giulietta Volante ◽  
Delaine D. Fadini ◽  
Julia Eichhorn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Surface ◽  
Hsp90 Inhibitor ◽  
Chemotherapeutic Drug ◽  
Therapeutic Approaches ◽  
Pediatric Solid Tumors ◽  
Tumor Research ◽  
And Migration ◽  
Emt Markers

Cancer stem cells (CSCs) are nowadays one of the major focuses in tumor research since this subpopulation was revealed to be a great obstacle for successful treatment. The identification of CSCs in pediatric solid tumors harbors major challenges because of the immature character of these tumors. Here, we present CD34, CD90, OV-6 and cell-surface vimentin (csVimentin) as reliable markers to identify CSCs in hepatoblastoma cell lines. We were able to identify CSC characteristics for the subset of CD34+CD90+OV-6+csVimentin+-co-expressing cells, such as pluripotency, self-renewal, increased expression of EMT markers and migration. Treatment with Cisplatin as the standard chemotherapeutic drug in hepatoblastoma therapy further revealed the chemo-resistance of this subset, which is a main characteristic of CSCs. When we treated the cells with the Hsp90 inhibitor 17-AAG, we observed a significant reduction in the CSC subset. With our study, we identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. This set of markers could be helpful to estimate the success of novel therapeutic approaches, as resistant CSCs are responsible for tumor relapses.

scholarly journals Therapeutic approaches targeting cancer stem cells

2018 ◽  
Vol 14 (7) ◽  
pp. 1469 ◽  
Author(s):  
Chuanwu Zhu ◽  
Yunzhi Pan ◽  
Sai Ma ◽  
Kaiyue Cao ◽  
Sufang Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Approaches
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