The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer: New challenges and therapeutic opportunities

Mehraj, Umar; Ganai, Rais A.; Macha, Muzafar A.; Hamid, Abid; Zargar, Mohammed A.; Bhat, Ajaz A.; Nasser, Mohd W.; Haris, Mohammad; Batra, Surinder K.; Alshehri, Bader; Al-Baradie, Raid Saleem; Mir, Manzoor Ahmad; Wani, Nissar Ahmad

doi:10.1007/s13402-021-00634-9

Cited by 83 publications

(39 citation statements)

References 218 publications

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“…In breast cancer, many immune-related pathways are abnormally regulated, thereby influencing the microenvironment, such as through immune cell infiltration [ 50 ]. Based on current literature, some believe that the TME is a potential treatment target in breast cancer [ 51 , 52 ]. To further demonstrate this conclusion, a drug sensitivity analysis was performed through which we identified significantly higher responses to agents, with the exception of lapatinib, in high-risk breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment-related multigene prognostic prediction model for breast cancer

Hong

Zhang

Yao

et al. 2022

Aging

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Background: Breast cancer is an invasive disease with complex molecular mechanisms. Prognosis-related biomarkers are still urgently needed to predict outcomes of breast cancer patients. Methods: Original data were download from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The analyses were performed using perl-5.32 and R-x64-4.1.1. Results: In this study, 1086 differentially expressed genes (DEGs) were identified in the TCGA cohort; 523 shared DEGs were identified in the TCGA and GSE10886 cohorts. Eight subtypes were estimated using non-negative matrix factorization clustering with significant differences seen in overall survival (OS) and progression-free survival (PFS) (P < 0.01). Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to develop a related risk score related to the 17 DEGs; this score separated breast cancer into low-and high-risk groups with significant differences in survival (P < 0.01) and showed powerful effectiveness (TCGA all group: 1-year area under the curve [AUC] = 0.729, 3-year AUC = 0.778, 5-year AUC = 0.781). A nomogram prediction model was constructed using non-negative matrix factorization clustering, the risk score, and clinical characteristics. Our model was confirmed to be related with tumor microenvironment. Furthermore, DEGs in high-risk breast cancer were enriched in histidine metabolism (normalized enrichment score [NES] = 1.49, P < 0.05), protein export (NES = 1.58, P < 0.05), and steroid hormone biosynthesis signaling pathways (NES = 1.56, P < 0.05). Conclusions: We established a comprehensive model that can predict prognosis and guide treatment.

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Section: Discussionmentioning

confidence: 99%

Tumor microenvironment-related multigene prognostic prediction model for breast cancer

Hong

Zhang

Yao

et al. 2022

Aging

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Section: Biological Function and Molecular Mechanism Of Circular Rnas In Glioblastomamentioning

confidence: 99%

“…Stem cells are widely involved in body growth and development and organ formation, and have the ability of self-renewal, infinite proliferation and multidirectional differentiation ( Jing et al, 2021 ; Mehraj et al, 2021 ; Mirzadeh Azad et al, 2021 ; Otero-Albiol and Carnero, 2021 ). The strong self-renewal ability, inherent high proliferative capacity and multidirectional differentiation together constitute the basic characteristics of malignant stem cells, among which the self-renewal ability is closely related to tumorigenesis and malignancy ( Ferragut et al, 2021 ; Mehraj et al, 2021 ; Yue et al, 2021 ). Over the past three to 4 decades, numerous studies have noted a potential link between stem cell systems and certain tumors, and a small proportion of tumor-initiating cells with stem cell properties, also known as tumor stem cells, have been identified in a variety of organs ( Cermeno and Garcia, 2016 ; Hass et al, 2020 ; Pan et al, 2021 ; Ryskalin et al, 2021 ).…”

Section: Biological Function and Molecular Mechanism Of Circular Rnas In Glioblastomamentioning

confidence: 99%

Research Progress of circRNAs in Glioblastoma

Guo

Piao

2021

Front. Cell Dev. Biol.

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Circular RNAs (circRNAs) are a class of single-stranded covalently closed non-coding RNAs without a 5′ cap structure or 3′ terminal poly (A) tail, which are expressed in a variety of tissues and cells with conserved, stable and specific characteristics. Glioblastoma (GBM) is the most aggressive and lethal tumor in the central nervous system, characterized by high recurrence and mortality rates. The specific expression of circRNAs in GBM has demonstrated their potential to become new biomarkers for the development of GBM. The specific expression of circRNAs in GBM has shown their potential as new biomarkers for GBM cell proliferation, apoptosis, migration and invasion, which provides new ideas for GBM treatment. In this paper, we will review the biological properties and functions of circRNAs and their biological roles and clinical applications in GBM.

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“…Besides the high expression of stemness and self-renewal markers, the aberrant expression of molecular signaling pathways including Wnt/β-catenin, Notch, Hedgehog, JAK-STAT, and PI3K/Akt/mTOR in BCSCs are shown to be involved in the pathophysiology of the disease [ 4 , 5 ]. Overall, the present literature reveals that the occurrence of BCSCs in the tumor microenvironment positively correlates with disease recurrence, low survival rate, chemo/radio therapy resistance, and low therapeutic output [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Breast Cancer-Derived Stem Cells by Dietary Phytochemicals: A Strategy for Cancer Prevention and Treatment

Prajapati

Gupta

Kumar

2022

Cancers

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Breast cancer is heterogeneous disease with variable prognosis and therapeutic response. Approximately, 70% of diagnosed breast cancer represents the luminal A subtype. This subpopulation has a fair prognosis with a lower rate of relapse than the other clinical subtypes. Acquisition of stemness in luminal A subtype modifies the phenotype plasticity to accomplish increased aggressiveness and therapeutic resistance. Therefore, targeting luminal A-derived breast cancer stem cells (BCSCs) could be a promising strategy for its prevention and treatment. Extensive studies reveal that dietary phytochemicals have the potential to target BCSCs by modulating the molecular and signal transduction pathways. Dietary phytochemicals alone or in combination with standard therapeutic modalities exert higher efficacy in targeting BCSCs through changes in stemness, self-renewal properties and hypoxia-related factors. These combinations offer achieving higher radio- and chemo- sensitization through alteration in the key signaling pathways such as AMPK, STAT3, NF-ĸB, Hedgehog, PI3K/Akt/mTOR, Notch, GSK3β, and Wnt related to cancer stemness and drug resistance. In this review, we highlight the concept of targeting luminal A-derived BCSCs with dietary phytochemicals by summarizing the pathways and underlying mechanism(s) involved during therapeutic resistance.

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The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer: New challenges and therapeutic opportunities

Cited by 83 publications

References 218 publications

Tumor microenvironment-related multigene prognostic prediction model for breast cancer

Tumor microenvironment-related multigene prognostic prediction model for breast cancer

Research Progress of circRNAs in Glioblastoma

Targeting Breast Cancer-Derived Stem Cells by Dietary Phytochemicals: A Strategy for Cancer Prevention and Treatment

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