Chemotherapy resistance and stromal targets in breast cancer treatment: a review

Spek, Y. M. van der; Kroep, JR; Tollenaar, Rob A.E.M.; Mesker, Wilma E.

doi:10.1007/s11033-020-05853-1

Cited by 24 publications

(19 citation statements)

References 55 publications

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“…Furthermore, focal adhesion kinase (FAK) signaling has also been related with the formation of fibrotic tumor microenvironment [172] and appears as a druggable target, not only in tumor cells but also in the tumor microenvironment [180]. The stromal targets list in BrCa is continually growing, as do newer therapies against stromal components [181,182]. For example, in vitro and in vivo approaches against the phosphodiesterase PDE5 (Sildenafil) or the nuclear receptors FXR (GW4064) have shown promising results due to their relevant role in CAFs biology and pro-tumoral effect [130,181,183,184].…”

Section: Targeting Cafs To Prevent Brca Progressionmentioning

confidence: 99%

“…The stromal targets list in BrCa is continually growing, as do newer therapies against stromal components [181,182]. For example, in vitro and in vivo approaches against the phosphodiesterase PDE5 (Sildenafil) or the nuclear receptors FXR (GW4064) have shown promising results due to their relevant role in CAFs biology and pro-tumoral effect [130,181,183,184].…”

Section: Targeting Cafs To Prevent Brca Progressionmentioning

confidence: 99%

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Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Fernández‐Nogueira

Fuster

Gutiérrez-Uzquiza

et al. 2021

Cancers

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Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.

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Section: Targeting Cafs To Prevent Brca Progressionmentioning

confidence: 99%

Section: Targeting Cafs To Prevent Brca Progressionmentioning

confidence: 99%

Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Fernández‐Nogueira

Fuster

Gutiérrez-Uzquiza

et al. 2021

Cancers

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“…In addition, the cure rates of the currently available BC treatment modalities are highly dependent on the molecular subtype of the tumor and the stage at diagnosis, which, in some cases, do not result in satisfactory clinical outcomes [ 5 ]. Inherent and/or acquired resistance to the existing hormonal and non-hormonal BC therapeutics is the main reason for BC therapy failure [ 6 , 7 ]. The great advances in understanding the biology and pathogenesis of BC lead to the development of targeted BC therapeutics.…”

Section: Introductionmentioning

confidence: 99%

The impact of CBP expression in estrogen receptor-positive breast cancer

et al. 2021

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Background The development of new biomarkers with diagnostic, prognostic and therapeutic prominence will greatly enhance the management of breast cancer (BC). Several reports suggest the involvement of the histone acetyltransferases CREB-binding protein (CBP) and general control non-depressible 5 (GCN5) in tumor formation; however, their clinical significance in BC remains poorly understood. This study aims to investigate the value of CBP and GCN5 as markers and/or targets for BC prognosis and therapy. Expression of CBP, GCN5, estrogen receptor α (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in BC was analyzed in cell lines by western blot and in patients’ tissues by immunohistochemistry. The gene amplification data were also analyzed for CBP and GCN5 using the publicly available data from BC patients. Results Elevated expression of CBP and GCN5 was detected in BC tissues from patients and cell lines more than normal ones. In particular, CBP was more expressed in luminal A and B subtypes. Using chemical and biological inhibitors for CBP, ERα and HER2 showed a strong association between CBP and the expression of ERα and HER2. Moreover, analysis of the CREBBP (for CBP) and KAT2A (for GCN5) genes in a larger number of patients in publicly available databases showed amplification of both genes in BC patients. Amplification of CREBBP gene was observed in luminal A, luminal B and triple-negative but not in HER2 overexpressing subtypes. Furthermore, patients with high CREBBP or KAT2A gene expression had better 5-year disease-free survival than the low gene expression group (p = 0.0018 and p < 0.00001, respectively). Conclusions We conclude that the persistent amplification and overexpression of CBP in ERα- and PR-positive BC highlights the significance of CBP as a new diagnostic marker and therapeutic target in hormone-positive BC.

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“…Many approaches which target BCAFs to enhance the efficacy of BC therapies have been proposed and pursued [ 168 ]. One such example is the use of vaccines to target the fibroblast activation protein alpha (FAPα), a protein specifically expressed by BCAFs [ 169 ].…”

Section: Breast Cancer Cell-stromal Interactions: Implications For Oncotherapymentioning

confidence: 99%

The Breast Tumor Microenvironment: A Key Player in Metastatic Spread

Terceiro

Edechi

Ikeogu

et al. 2021

Cancers

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The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior. In this review, we will highlight recent advances in our current knowledge about the multiple interactions between breast cancer cells and neighboring cells (fibroblasts, endothelial cells, adipocytes, innate and adaptive immune cells) in the tumor microenvironment that coordinate to regulate metastasis. We also highlight the role of exosomes and circulating tumor cells in facilitating breast cancer metastasis. We discuss some key markers associated with stromal cells in the breast tumor environment and their potential to predict patient survival and guide treatment. Finally, we will provide some brief perspectives on how current technologies may lead to the development of more effective therapies for the clinical management of breast cancer patients.

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Chemotherapy resistance and stromal targets in breast cancer treatment: a review

Cited by 24 publications

References 55 publications

Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

The impact of CBP expression in estrogen receptor-positive breast cancer

The Breast Tumor Microenvironment: A Key Player in Metastatic Spread

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