Recent advances in therapeutic strategies for triple-negative breast cancer

Li, Yun; Zhang, Huajun; Merkher, Yulia; Chen, Lin; Liu, Na; Leonov, Sergey; Chen, Yongheng

doi:10.1186/s13045-022-01341-0

Cited by 319 publications

(213 citation statements)

References 175 publications

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“…Overall, our results together with others provide further evidence that C1QBP has a significant role in maintaining metabolic activities, and that its depletion leads to alterations in cellular metabolism and reduced cell proliferation. Thus far, several targeted agents such as inhibitors for poly(ADP-ribose) polymerase, vascular endothelial growth factor receptors, epidermal growth factor receptors, ras/raf/mitogen activated protein kinase, phosphatidylinositol 3-kinase, IGF 1, histone deacetylase, and heat shock protein 90, are being explored as potential therapeutic targets for breast cancer, with many of them in clinical trials [ 9 , 55 ]. Given that C1QBP is associated with proliferation and implicated in lipid metabolism and BCAAs, future studies using clinical samples and cutting-edge omics technologies are necessary to pave the way for the identification of C1QBP-based theranostics for breast cancer, which may add to the therapeutic landscape of TNBC [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…Despite conventional therapy, the overall survival of TNBC patients is shorter as a result of metastasis and treatment failure due to chemoresistance [ 8 ]. Recently, several novel agents have been developed to treat breast cancer [ 9 ], but there is still a pressing need for efficacious therapeutic strategies to increase the survival of these patients. The advent of precision oncology has led to the discovery of dysfunctional signaling pathways and anomalous protein expression in patients with TNBC, which have shown promise as novel therapeutic targets [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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C1QBP Mediates Breast Cancer Cell Proliferation and Growth via Multiple Potential Signalling Pathways

Scully

Sudhaharan

Matsumoto

et al. 2023

IJMS

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Breast carcinoma is the most prevalent cancer in women globally, with complex genetic and molecular mechanisms that underlie its development and progression. Several challenges such as metastasis and drug resistance limit the prognosis of breast cancer, and hence a constant search for better treatment regimes, including novel molecular therapeutic targets is necessary. Complement component 1, q subcomponent binding protein (C1QBP), a promising molecular target, has been implicated in breast carcinogenesis. In this study, the role of C1QBP in breast cancer progression, in particular cancer cell growth, was determined in triple negative MDA-MB-231 breast cancer cells. Depletion of C1QBP decreased cell proliferation, whereas the opposite effect was observed when C1QBP was overexpressed in MDA-MB-231 cells. Furthermore, gene expression profiling and pathway analysis in C1QBP depleted cells revealed that C1QBP regulates several signaling pathways crucial for cell growth and survival. Taken together, these findings provide a deeper comprehension of the role of C1QBP in triple negative breast cancer, and could possibly pave the way for future advancement of C1QBP-targeted breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C1QBP Mediates Breast Cancer Cell Proliferation and Growth via Multiple Potential Signalling Pathways

Scully

Sudhaharan

Matsumoto

et al. 2023

IJMS

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“…Cancer is a major disease that threatens billions of lives worldwide [ 34 ]. It is difficult to diagnose in early stages, and late stage metastasis makes it the number one killer of human beings [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Pancancer Analysis of the Prognostic and Immunotherapeutic Value of Progestin and AdipoQ Receptor 4

Yang

Zhu

et al. 2022

Computational and Mathematical Methods in Medicine

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AdipoQ receptor 4 (PAQR4) belongs to the family of progestin and AdipoQ receptors. PAQR4 plays an oncogenic role in lung and breast cancer. However, systematic pancancer analyses of PAQR4 have not been performed. The purpose was to investigate the prognostic and immunological significance of PAQR4 across 31 tumor types. Data were obtained from the following sources: TCGA, GEO, UALCAN, TIMER, GEPIA2, KM plotter, and TISIDB databases. The results proved that PAQR4 expression was significantly elevatory in most cancer types. We then explored the utility of PAQR4 as a prognostic indicator across all cancers. Using Cox proportional risk regression models, it has been demonstrated that PAQR4 is an independent risk factor in. High PAQR4 expression was not associated with other prognostic indicators, including overall survival, disease-free interval, disease-specific survival, and progression-free period. Subsequently, we explored the immunological value of PAQR4 and found that PAQR4 expression significantly correlated with tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoint genes in tumors. It also significantly negatively correlated with most tumors’ ESTIMATE scores, indicating that PAQR4 can influence the cellular composition of the tumor microenvironment. Our findings suggest the immunotherapeutic potential of PAQR4 in tumors. Finally, we explored the role of PAQR4 in tumor drug resistance and found that PAQR4 expression affected the sensitivity to multiple chemotherapeutic agents. A significant role for PAQR4 in tumor immunity is evident in these studies, as well as its potential role in cancer diagnosis, prognosis, and treatment precision.

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“…It is well known that the tumor immune microenvironment (TIME) contains numerous tumor-in ltrating lymphocytes (TILs) and plays an indispensable role in antitumor immunity and tumor progression in TNBC [10][11][12]. Unfortunately, the obvious bene ts of antitumor immunotherapy remain limited to a small subset of individuals with TNBC [13,14]. These limitations must be resolved to e ciently induce the host antitumor immune response [15].…”

Section: Introductionmentioning

confidence: 99%

Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy

Huang¹,

Wang

Jiang

et al. 2023

Preprint

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Cancer-associated adipocytes (CAAs), one of the primary stromal components, exhibit intimate crosstalk and release multiple cell factors mediating local and systemic biological effects. However, the role of CAAs in the regulation of systemic immune responses and their potential value in the clinical treatment of triple-negative breast cancer (TNBC) are not well described. Transcriptome sequencing was performed on CAA and normal adipocyte (NA) tissues isolated from surgically resected samples from TNBC patients and healthy controls. Cytokines, including C-X-C motif chemokine ligand 8 (CXCL8, also known as IL-8), secreted from NAs and CAAs were compared by transcriptome sequencing and enzyme-linked immunosorbent assay (ELISA). Proliferation, migration and invasion assays were employed to analyze the role of CAAs and CAA-derived CXCL8 (macrophage inflammatory protein-2 (MIP2) as a functional surrogate in mice). TNBC syngraft models were established to evaluate the curative effect of targeting CXCL8 in combination with anti-PD-1 therapies. Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), polymerase chain reaction (PCR) array, flow cytometry, immunohistochemistry (IHC), and immunofluorescence (IF) were applied to analyze immune cell infiltration and epithelial-mesenchymal transition (EMT) markers. Specifically, we demonstrated that CAAs and CAA-derived CXCL8 played important roles in tumor growth, EMT, metastasis and tumor immunity suppression. CAA-derived CXCL8 remodeled the tumor immune microenvironment not only by suppressing CD4+ T and CD8+ T immune cell infiltration but also by upregulating PD-L1 expression in TNBC. The combination of targeting CXCL8 pathway and blocking PD-1 pathway synergistically increased the tumor immune response and inhibited tumor progression. Thus, our results highlight the molecular mechanisms and translational significance of CAAs in tumor progression and immune ecosystem regulatory effects and provide a better understanding of the potential clinical benefit of targeting CAA-derived CXCL8 in antitumor immunity and as a new therapeutic moiety in TNBC.

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Recent advances in therapeutic strategies for triple-negative breast cancer

Cited by 319 publications

References 175 publications

C1QBP Mediates Breast Cancer Cell Proliferation and Growth via Multiple Potential Signalling Pathways

C1QBP Mediates Breast Cancer Cell Proliferation and Growth via Multiple Potential Signalling Pathways

Pancancer Analysis of the Prognostic and Immunotherapeutic Value of Progestin and AdipoQ Receptor 4

Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy

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