Evaluation of treatment outcomes of triple-negative breast cancer

Cinkaya, Ahmet; Akın, Mustafa; Sengul, Adem

doi:10.4103/0973-1482.154000

Cited by 23 publications

(10 citation statements)

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“…Breast cancer is the most common cancer among women and the leading cause of cancer-related death worldwide. Despite advances in molecular classification and targeted molecular therapy, breast cancer incidence and mortality rate remain high [ 1 – 5 ]. TNBC is a subset of the basal-like breast cancer group, characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and Her-2/EGFR2 [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways

et al. 2017

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The Hippo pathway is an evolutionarily conserved signaling pathway that regulates proliferation and apoptosis to control organ size during developmental growth. Yes-associated protein 1 (YAP1), the terminal effector of the Hippo pathway, is a transcriptional co-activator and a potent growth promoter that has emerged as a critical oncogene. Overexpression of YAP1 has been implicated in promoting resistance to chemo-, radiation and targeted therapy in various cancers. However, the role of YAP1 in radioresistance in triple-negative breast cancer (TNBC) is currently unknown. We evaluated the role of YAP1 in radioresistance in TNBC in vitro, using two approaches to inhibit YAP1: 1) genetic inhibition by YAP1 specific shRNA or siRNA, and 2) pharmacological inhibition by using the small molecule inhibitor, verteporfin that prevents YAP1 transcriptional activity. Our findings demonstrate that both genetic and pharmacological inhibition of YAP1 sensitizes TNBC cells to radiation by inhibiting the EGFR/PI3K/AKT signaling axis and causing an increased accumulation of DNA damage. Our results reveal that YAP1 activation exerts a protective role for TNBC cells in radiotherapy and represents a pharmacological target to enhance the anti-tumor effects of DNA damaging modalities in the treatment of TNBC.

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Section: Introductionmentioning

confidence: 99%

YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways

et al. 2017

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“…Hence, understanding the molecular mechanisms underlying distant metastasis and early relapse of TNBC is pivotal to discover new therapeutic targets and improve prognosis of these patients. Potential pre-treatment values of different molecular markers have been identified, such as androgen receptors (AR), basal cytokeratin, and BRCA genes [7]. Unfortunately, currently none of them can be recognized as a real effective diagnostic or treatment target for TNBC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-455-3p promotes invasion and migration in triple negative breast cancer by targeting tumor suppressor EI24

Meng

Pan

et al. 2016

Oncotarget

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Lacking of treatment methods for the patients with triple negative breast cancer (TNBC) underscores the pivotal needs to further understand its biology as well as to find better biomarkers and develop novel therapeutic strategies. Increasing evidences support that aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis and may serve as biomarkers for diagnostic and prognostic purposes of various cancers. In current study, we found that miR-455-3p and miR-196a-5p were intensively overexpressed in TNBC compared with the hormone receptor (HR) positive breast cancer whereas miR-425-5p was down-regulated by miRNA microarray analysis. qRT-PCR analysis confirmed that the expression of miR-455-3p in TNBC cell lines MDA-MB-231 and MDA-MB-468 was higher than that in HR positive breast cancer cell line MCF-7(p<0.01). Functional experiments in vitro showed that miR-455-3p enhanced cell proliferative, invasive and migrational abilities in TNBC cell lines. miRNA targets prediction showed SMAD2, LTBR and etoposide induced 2.4 (EI24) were potential target genes of miR-455-3p, and then it was confirmed by qRT-PCR assay. Dual luciferase reporter assay showed the specific binding of miR-455-3p to 3′ UTR of EI24 in TNBC. Then we found miR-455-3p inhibited the EI24 expression at the levels of mRNA and protein. Through small interfering RNA (siRNA) targeting EI24 gene, there were strengthened capabilities of invasion and migration of TNBC cells, and increased expression of EI24 had the inverse effects. In conclusion, the data suggest that miRNA455-3p promotes invasion and migration by targeting tumor suppressor EI24 and might be a potential prognostic biomarker and therapeutic target in TNBC.

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“…Although TNBC patients initially respond to neoadjuvant treatments, only 30% of them will exhibit a survival higher than 5-years following the first diagnosis, reflecting the aggressiveness of this subtype [ 23 , 24 ]. Patients with BRCA1 mutation are often diagnosed with TNBC but not all TNBC are BRCA1 positive.…”

Section: Triple Negative Breast Cancermentioning

confidence: 99%

Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

et al. 2016

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Breast cancer is one of the most widespread carcinoma and one of the main causes of cancer-related death worldwide, especially in women aged between 35 and 75 years. Among the different subtypes, triple negative breast cancer (TNBC) is characterized by the total absence of the estrogen-receptor (ER) and progesteron-receptor (PR) expression as well as the lack of human epidermal growth factor receptor 2 (HER2) overexpression or gene amplification. These biological characteristics confer to TNBC a higher aggressiveness and relapse risk along with poorer prognosis compared to other subtypes. Indeed, 5-years survival rate is still low and almost all patients die, despite any adjuvant treatment which at moment represents the heading pharmacological approach. To date, several clinical trials have been designed to investigate the potential role of some molecular markers, such as VEGF, EGFR, Src and mTOR, for targeted treatments in TNBC. In fact, many inhibitors of the PI3K/AKT/mTOR pathway, frequently de-regulated in TNBC, are acquiring a growing interest and several inhibitors are in preclinical development or already in early phase clinical trials. In this Review, we investigated the role of the PI3K/AKT/mTOR pathway in TNBC patients, by summarizing the molecular features that led to the distinction of different histotypes of TNBC. Furthermore, we provided an overview of the inhibition mechanisms of the mTOR and PI3K/AKT signaling pathways, highlighting the importance of integrating biological and clinical data for the development of mTOR inhibitors in order to implement targeted therapies for TNBC patients.

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Evaluation of treatment outcomes of triple-negative breast cancer

Cited by 23 publications

References 0 publications

YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways

YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways

MicroRNA-455-3p promotes invasion and migration in triple negative breast cancer by targeting tumor suppressor EI24

Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

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