An insight into the cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer

2021 ◽  
Author(s):  
Hina Qayoom ◽  
Nissar A Wani ◽  
Bader Alshehri ◽  
Manzoor A Mir

Triple-negative breast cancer (TNBC) is the most complex, aggressive and fatal subtype of breast cancer. Owing to the lack of targeted therapy and heterogenic nature of TNBC, chemotherapy remains the sole treatment option for TNBC, with taxanes and anthracyclines representing the general chemotherapeutic regimen in TNBC therapy. But unfortunately, patients develop resistance to the existing chemotherapeutic regimen, resulting in approximately 90% treatment failure. Breast cancer stem cells (BCSCs) are one of the major causes for the development of chemoresistance in TNBC patients. After surviving the chemotherapy damage, the presence of BCSCs results in relapse and recurrence of TNBC. Several pathways are known to regulate BCSCs’ survival, such as the Wnt/β-catenin, Hedgehog, JAK/STAT and HIPPO pathways. Therefore it is imperative to target these pathways in the context of eliminating chemoresistance. In this review we will discuss the novel strategies and various preclinical and clinical studies to give an insight into overcoming TNBC chemoresistance. We present a detailed account of recent studies carried out that open an exciting perspective in relation to the mechanisms of chemoresistance.

2021 ◽  
Author(s):  
Kevin Chappell ◽  
Kanishka Manna ◽  
Charity L. Washam ◽  
Stefan Graw ◽  
Duah Alkam ◽  
...  

Multi-omics data integration of triple negative breast cancer (TNBC) provides insight into biological pathways.


2020 ◽  
Vol 21 (23) ◽  
pp. 8905
Author(s):  
Amal Qattan

Treatment of triple-negative breast cancer (TNBC) remains challenging because of the heterogeneity of the disease and lack of single targetable driving mutations. TNBC does not rely on estrogen, progesterone or epidermal growth factor receptors and is associated with aggressive disease progression and poor prognosis. TNBC is also characterized by resistance to chemotherapeutics, and response to immunotherapies is limited despite promising results in a subset of TNBC patients. MicroRNAs (miRNAs) have emerged as significant drivers of tumorigenesis and tumor progression in triple-negative breast cancer (TNBC) and present unique opportunities to target various components of the TNBC microenvironment for improved efficacy against this difficult to treat cancer. Effects of miRNAs on multiple targets may improve response rates in the context of this genetically and biologically heterogeneous disease. In this review, we offer a comprehensive view of miRNA regulation in TNBC, treatment challenges presented by TNBC in the context of the tumor microenvironment and stem cell subpopulations, and current and emerging miRNA-based therapeutic strategies targeting various components of the TNBC microenvironment. In addition, we offer insight into novel targets that have potential for treating TNBC through multiple mechanisms in the tumor microenvironment simultaneously and those that may be synergistic with standard chemotherapies.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 929
Author(s):  
Dima Hattab ◽  
Athirah Bakhtiar

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer. Owing to the absenteeism of hormonal receptors expressed at the cancerous breast cells, hormonal therapies and other medications targeting human epidermal growth factor receptor 2 (HER2) are ineffective in TNBC patients, making traditional chemotherapeutic agents the only current appropriate regimen. Patients’ predisposition to relapse and metastasis, chemotherapeutics’ cytotoxicity and resistance and poor prognosis of TNBC necessitates researchers to investigate different novel-targeted therapeutics. The role of small interfering RNA (siRNA) in silencing the genes/proteins that are aberrantly overexpressed in carcinoma cells showed great potential as part of TNBC therapeutic regimen. However, targeting specificity, siRNA stability, and delivery efficiency cause challenges in the progression of this application clinically. Nanotechnology was highlighted as a promising approach for encapsulating and transporting siRNA with high efficiency-low toxicity profile. Advances in preclinical and clinical studies utilizing engineered siRNA-loaded nanotherapeutics for treatment of TNBC were discussed. Specific and selective targeting of diverse signaling molecules/pathways at the level of tumor proliferation and cell cycle, tumor invasion and metastasis, angiogenesis and tumor microenvironment, and chemotherapeutics’ resistance demonstrated greater activity via integration of siRNA-complexed nanoparticles.


2015 ◽  
Vol 151 (2) ◽  
pp. 281-294 ◽  
Author(s):  
Masaya Kai ◽  
Noriko Kanaya ◽  
Shang V. Wu ◽  
Carlos Mendez ◽  
Duc Nguyen ◽  
...  

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