The Landscape of Targeted Therapies in TNBC

Vagia, Elena; Mahalingam, Devalingam; Cristofanilli, Massimo

doi:10.3390/cancers12040916

Cited by 301 publications

(213 citation statements)

References 136 publications

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“…Numerous studies have focused on the identification and characterization of the aberrant signaling pathways involved in the aggressive features of TNBCs [ 85 , 86 ]. In this vein, the amplification of the FGFR1 and FGFR2 gene loci has been described as recurrent in this breast cancer subtype [ 38 , 42 ].…”

Section: Deregulation Of Fgf/fgfr Signaling Across Breast Cancer Smentioning

confidence: 99%

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Santolla

Maggiolini

2020

Cancers

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One of the major challenges in the treatment of breast cancer is the heterogeneous nature of the disease. With multiple subtypes of breast cancer identified, there is an unmet clinical need for the development of therapies particularly for the less tractable subtypes. Several transduction mechanisms are involved in the progression of breast cancer, therefore making the assessment of the molecular landscape that characterizes each patient intricate. Over the last decade, numerous studies have focused on the development of tyrosine kinase inhibitors (TKIs) to target the main pathways dysregulated in breast cancer, however their effectiveness is often limited either by resistance to treatments or the appearance of adverse effects. In this context, the fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) system represents an emerging transduction pathway and therapeutic target to be fully investigated among the diverse anti-cancer settings in breast cancer. Here, we have recapitulated previous studies dealing with FGFR molecular aberrations, such as the gene amplification, point mutations, and chromosomal translocations that occur in breast cancer. Furthermore, alterations in the FGF/FGFR signaling across the different subtypes of breast cancer have been described. Next, we discussed the functional interplay between the FGF/FGFR axis and important components of the breast tumor microenvironment. Lastly, we pointed out the therapeutic usefulness of FGF/FGFR inhibitors, as revealed by preclinical and clinical models of breast cancer.

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Section: Deregulation Of Fgf/fgfr Signaling Across Breast Cancer Smentioning

confidence: 99%

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Santolla

Maggiolini

2020

Cancers

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“…Compared with other types of breast cancer, TNBC is characterized by high malignancy rate, easier recurrence (Dent et al 2007), and low survival rate (Carey et al 2006). Despite advances in the targeted therapies of TNBC, including the approval of poly-ADP-ribose polymerase (PARP) and immune check-point inhibitors for the treatment of BRCA germ cell mutated breast cancers, there is still a lack of clinical evidence to evaluate their efficacy for TNBC patients (Vagia et al 2020). Therefore, it is necessary to identify effective molecular therapeutic targets for TNBC.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Identification of NUF2 and FAM83D as potential biomarkers in triple-negative breast cancer (v0.2)"

2020

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Background. Breast cancer is a heterogeneous disease. Compared with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is easy to metastasize and has a short survival time, less choice of treatment options. Here, we aimed to identify the potential biomarkers to TNBC diagnosis and prognosis. Material/Methods. Three independent data sets (GSE45827, GSE38959, GSE65194) were downloaded from the Gene Expression Omnibus (GEO). The R software packages were used to integrate the gene profiles and identify differentially expressed genes (DEGs). A variety of bioinformatics tools were used to explore the hub genes, including the DAVID database, STRING database and Cytoscape software. Reverse transcription quantitative PCR (RT-qPCR) was used to verify the hub genes in 14 pairs of TNBC paired tissues. Results. In this study, we screened out 161 DEGs between 222 non-TNBC and 126 TNBC samples, of which 105 genes were up-regulated and 56 were down-regulated. These DEGs were enriched for 27 GO terms and 2 pathways. GO analysis enriched mainly in "cell division", "chromosome, centromeric region" and "microtubule motor activity". KEGG pathway analysis enriched mostly in "Cell cycle" and "Oocyte meiosis". PPI network was constructed and then 10 top hub genes were screened. According to the analysis results of the Kaplan-M eier survival curve, the expression levels of only NUF2, FAM83D and CENPH were associated with the recurrence-free survival in TNBC samples (P<0.05). RT-qPCR confirmed that the expression levels of NUF2 and FAM83D in TNBC tissues were indeed up-regulated significantly. Conclusions. The comprehensive analysis showed that NUF2 and FAM83D could be used as potential biomarkers for diagnosis and prognosis of TNBC.

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“…Clinically, BC is categorized into three basic therapeutic groups: (i) The ER positive, (ii) the HER2 positive, and (iii) the triple negative (ER/PR/HER2 negative, where PR stands for progesterone receptor) for which no targeted therapy is currently available [100], besides chemotherapy.…”

Section: Breast Cancermentioning

confidence: 99%

Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research

Herrmann

Bernasconi

McCarthy

et al. 2020

Animals

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Dementia and cancer are becoming increasingly prevalent in Western countries. In the last two decades, research focused on Alzheimer’s disease (AD) and cancer, in particular, breast cancer (BC) and prostate cancer (PC), has been substantially funded both in Europe and worldwide. While scientific research outcomes have contributed to increase our understanding of the disease etiopathology, still the prevalence of these chronic degenerative conditions remains very high across the globe. By definition, no model is perfect. In particular, animal models of AD, BC, and PC have been and still are traditionally used in basic/fundamental, translational, and preclinical research to study human disease mechanisms, identify new therapeutic targets, and develop new drugs. However, animals do not adequately model some essential features of human disease; therefore, they are often unable to pave the way to the development of drugs effective in human patients. The rise of new technological tools and models in life science, and the increasing need for multidisciplinary approaches have encouraged many interdisciplinary research initiatives. With considerable funds being invested in biomedical research, it is becoming pivotal to define and apply indicators to monitor the contribution to innovation and impact of funded research. Here, we discuss some of the issues underlying translational failure in AD, BC, and PC research, and describe how indicators could be applied to retrospectively measure outputs and impact of funded biomedical research.

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The Landscape of Targeted Therapies in TNBC

Cited by 301 publications

References 136 publications

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Peer Review #2 of "Identification of NUF2 and FAM83D as potential biomarkers in triple-negative breast cancer (v0.2)"

Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research

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