scholarly journals Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

2021 ◽  
Author(s):  
Andrew Sulaiman ◽  
Sarah McGarry ◽  
Sai Chilumula ◽  
Rohithk Kandunuri ◽  
Vishak Vinod
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Treatment Strategies ◽  
Major Barrier ◽  
Differential Signal ◽  
Popula Tions ◽  
Novel Treatment Strategies ◽  
Patient Prognosis

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these popula-tions remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and discusses novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

scholarly journals Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

2021 ◽  
Author(s):  
Andrew Sulaiman ◽  
Sarah McGarry ◽  
Sai Charan Chilumula ◽  
Vishak Vinod ◽  
Rohith Kandunuri
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Treatment Strategies ◽  
Major Barrier ◽  
Differential Signal ◽  
Growth Factor Beta ◽  
Novel Treatment Strategies ◽  
Patient Prognosis

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

scholarly journals Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1386
Author(s):  
Andrew Sulaiman ◽  
Sarah McGarry ◽  
Sai Charan Chilumula ◽  
Rohith Kandunuri ◽  
Vishak Vinod
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Treatment Strategies ◽  
Major Barrier ◽  
Differential Signal ◽  
Growth Factor Beta ◽  
Novel Treatment Strategies ◽  
Patient Prognosis

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC, which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24−) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation, which may lead to the development of novel therapies to improve TNBC patient prognosis.

scholarly journals Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zihe Guo ◽  
Ayao Guo ◽  
Chuang Zhou
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Treatment Strategies ◽  
Dependent Manner ◽  
Promote Cell Migration ◽  
Cancer Aggressiveness ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms

Continuous chemotherapy pressure-elicited annexin-A6 (ANXA6)-containing exosome (ANXA6-exo) secretion contributes to paclitaxel (PTX) resistance in breast cancer (BC), but the molecular mechanisms are not fully elucidated. The present study managed to investigate this issue and found that ANXA6-exo promoted PTX resistance and cancer progression in BC cells in a Yes-associated protein 1 (YAP1)-dependent manner. Specifically, the parental PTX-sensitive BC (PS-BC) cells were exposed to continuous low-dose PTX to generate PTX-resistant BC (PR-BC) cells, and we found that BC stem cells tended to be enriched in the descendent PR-BC cells in contrast with the PS-BC cells. In addition, PR-BC cell-derived exosomes were featured with highly expressed ANXA6, and ANXA6-exo delivered ANXA6 to promote cell migration, growth, autophagy, and stemness in PS-BC cells. Interestingly, ANXA6-exo increased PTX resistance in PS-BC cells via inducing autophagy, and the effects of ANXA6-exo on PTX resistance in PS-BC cells were abrogated by co-treating cells with the autophagy inhibitor 3-methyladenine. Moreover, the underlying mechanisms were uncovered, and we evidenced that ANXA6-exo up-regulated YAP1 to promote Hippo pathway dysregulation, and the promoting effects of ANXA6-exo on PTX resistance and cancer aggressiveness in BC cells were abrogated by silencing YAP1. Taken together, this study firstly elucidated the underlying mechanisms by which BCSC-derived ANXA6-exo facilitated BC progression and PTX resistance, which might help to develop novel treatment strategies for BC in clinic.

Expanding the Biotherapeutics Realm via miR-34a: “Potent Clever Little” Agent in Breast Cancer Therapy

2019 ◽  
Vol 20 (8) ◽  
pp. 665-673 ◽  
Author(s):  
Mohsen Mohammady ◽  
Seyed I. Ghetmiri ◽  
Mahtab Baharizade ◽  
Mohammad H. Morowvat ◽  
Susan Torabi
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Tumor Suppressor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Signal Pathways ◽  
Breast Cancer Therapy ◽  
Female Population ◽  
Therapeutic Goals ◽  
Normal Tissues

Background:One of the most prevalent cancers befell to women is considered to be breast cancer (BC). It is also the deadliest among the female population after lung cancer. Additionally, several studies have demonstrated that there is an association between microRNA34-a and breast cancer.Method:We searched PubMed, Web of Science, and Google Scholar up to December 2018. Those studies which have been studied miR-34a and its tumor-suppressing capabilities were considered as the most important topics. Moreover, we extracted articles which were solely focused on microRNA-34a in breast cancer therapy. Finally, 80 articles were included.Results:In comparison with the normal tissues, down-regulation of miR-34a expression is shown considerably in tumor cells. Overexpression of miR-34a acts as a tumor suppressor by transcriptional regulating one of the signaling pathways (TP53), NOTCH, and transforming growth factor beta (TGF-β), Bcl- 2 and SIRT1genes, HDAC1 and HDAC7, Fra-1, TPD52, TLR Via CXCL10. Moreover, drug resistance declines which lead to the apoptosis, cell cycle arrest and senescence. As a result, the proliferation, invasion and metastasis of the tumor are suppressed. The Mrx34 drug contains miR-34a mimic and a lipid vector. MiR-34a as the active ingredient portrays the role of a tumor suppressor. This drug has recently entered the clinical trials studies.Conclusion:These findings suggest a robust cause for developing miR-34a as a therapeutic agent to target BC. In that scenario, miR-34a is strongly useful to introduce new therapeutic goals for BC. Moreover, this review aims to confirm the signal pathways, therapeutic and diagnostic values of miR- 34a in BC and beyond.

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