Trastuzumab and survival of patients with metastatic breast cancer

Kast, Karin; Schoffer, Olaf; Link, Theresa; Forberger, A; Petzold, A; Niedostatek, Antje; Werner, C.; Klug, Stefanie J.; Werner, A.; Gatzweiler, A.; Richter, Barbara; Baretton, Gustavo; Wimberger, Pauline

doi:10.1007/s00404-017-4421-x

Cited by 24 publications

(21 citation statements)

References 27 publications

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“…Targeted therapeutic drugs could aim different genes and signalling pathways in breast cancer. For example, agents targetin estrogen receptor (ER) and hER2, such as tamoxifen and trastuzumab, are the most extensively used therapeutics in breast cancer (31,32). These therapeutic drugs have therefore been designed for different molecular subtypes.…”

Section: Discussionmentioning

confidence: 99%

miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R

et al. 2020

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The long non-coding (lnc)RNA named tissue differentiation inducing non-protein coding RNA (TINcR) is a tumor marker that has not been studied in breast cancer. The present study aimed to investigate the TINcR-targeting micro (mi)RNAs and the regulatory mechanisms of TINcR in breast cancer. Following prediction by TargetScan and confirmation by dual-luciferase reporter assay, TINcR was demonstrated to be a target gene for miR-589-3p. The expression of TINcR and miR-589-3p in breast cancer and adjacent tissues was detected by reverse transcription-quantitative (RT-q)PcR, and the correlation between TINcR and miR-589-3p expression was determined by using Spearman correlation analysis. The 5-years survival was analyzed in patients with breast cancer according to TINcR expression (high or low). The effects of TINcR and miR-589-3p on the proliferation, apoptosis, migratory and invasive abilities of some breast cancer cell lines were detected by MTT assay, flow cytometry, wound healing assay and Transwell assay. The target gene of miR-589-3p was predicted and verified by TargetScan and dual-luciferase reporter assay, and the mechanism of miR-589-3p involvement in breast cancer cells was explored by overexpression or downregulation of miR-589-3p in breast cancer cells. RT-qPcR and western blotting were used to determine the expression of the insulin-like growth factor 1 receptor (IGF1R)/AKT pathway-related genes. The results demonstrated that TINcR expression level was negatively correlated with miR-589-3p expression level in breast cancer tissues and that patients with high expression of TINcR presented with lower survival rates. In addition, TINcR overexpression in cancer cells inhibited miR-589-3p expression, and cell transfection with miR-589-3p mimic partially reversed the effect of TINcR overexpression on the promotion of cancer cell proliferation, migration and invasion, and on the inhibition of cancer cell apoptosis. Furthermore, IGF1R, which is a target gene of miR-589-3p, increased cancer cell proliferation, migration and invasion and inhibited cancer cell apoptosis; however, these effects were partially reversed by miR-589-3p mimic. Furthermore, the results demonstrated that miR-589-3p mimic could downregulate the protein expression of IGF1R and p-AKT. In addition, TINcR overexpression downregulated miR-589-3p expression level. miR-589-3p partially reversed the effects of TINcR overexpression on cancer cell proliferation, migration and invasion, and inhibited cancer cell apoptosis by inhibiting the IGF1R-Akt pathway. The results from the present study demonstrated that TINcR may sponge miR-589-3p in order to inhibit IGF1R-Akt pathway activation in breast cancer cells, promoting therefore cancer cell proliferation, migration and invasion.

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Section: Discussionmentioning

confidence: 99%

miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R

et al. 2020

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“…Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) have been therapeutic targets for drug development in the treatment of BC . ER‐targeted agents such as tamoxifen and raloxifene, and HER2‐targeted agents, including trastuzumab and lapatinib have shown substantial therapeutic benefits in BC. However, a majority of current treatment strategies are ineffective due to de novo or acquired resistance .…”

Section: Introductionmentioning

confidence: 99%

2′‐Hydroxyflavanone inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP76

Singhal

Chikara

Horne

et al. 2018

Molecular Carcinogenesis

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Consumption of citrus-fruits is associated with reduced incidence of breast cancer (BC), the most common cancer diagnosed in women across the globe. In this study, we investigated the anticancer potential of 2-Hydroxyflavanone (2HF) in BC. 2HF, a citrus-bioflavonoid, has demonstrated anticancer properties in various cancers, but its anticancer role in BC has not been well studied. We investigated the in vitro and in vivo growth inhibitory effects of 2HF in an array of BC lines and in xenograft mouse models of ER-positive and HER2-positive BC cells. Compared to control, 2HF treatment reduced cell viability and suppressed migratory and invasive potential of BC cells, while, no growth inhibitory effects were observed in non-tumorigenic breast epithelial cells. Further, 2HF inhibited the expression of RLIP76, a stress-defensive and anti-apoptotic protein, which is over-expressed in BC cells and simultaneously reduced proliferation of BC cells. Nude mice bearing MCF7 or SKBR3 BC cells xenografts treated with either 2HF or targeting RLIP76 by RLIP76-antisense or RLIP76-antibody treatment had significantly lower tumor-weight as compared to corresponding controls. In addition, Western-blotting and immunohistochemical analysis of tumor tissue from control and treatment group mice showed that 2HF decreased protein expression levels of RLIP76, and the decrease was similar to those seen following RLIP76-antisense treatment. Furthermore, 2HF decreased expression of Ki67, CD31, vimentin, inhibited phosphorylation of Akt and expression of survivin and Bcl2, and increased levels of Bax, E-cadherin, and cleaved-PARP. Therefore, our results indicate that 2HF may suppress BC growth in vitro and in vivo by targeting RLIP76, and may serve as a potential adjuvant treatment in BC patients.

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“…Although the survival rate of breast cancer patients has been increased by molecular targeted therapies against HER2 or hormone receptors 1–3 , TNBC is associated with the worst prognosis 4 , and TNBC patients show relapse and frequently develop metastasis in visceral organs.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of cathepsin S and matrix metalloproteinase-9 via Src, a non-receptor tyrosine kinase, suppresses triple-negative breast cancer growth and metastasis

et al. 2018

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Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer with poor prognosis. In the present study, we demonstrated that Src, a non-receptor tyrosine kinase, might provide an effective therapeutic strategy to overcome TNBC invasion and metastasis, which are mediated via the synergistic action of the lysosomal enzyme cathepsin S (CTSS) and gelatinase MMP-9. Knock-down of MMP-9 and CTSS using siRNAs resulted in a synergistic suppression of MDA-MB-231 cell invasion, which was similarly observed with pharmacological inhibitors. During the screening of new drug candidates that suppress both CTSS and MMP-9, BJ-2302, a novel 7-azaindolin-2-one derivative, was discovered. Src, an upstream activator of both pathways (PI3K/Akt and Ras/Raf/ERK) responsible for the expression of CTSS and MMP-9, was identified as a high-affinity target of BJ-2302 (IC90: 3.23 µM) through a Src kinase assay and a drug affinity responsive target stability (DARTS) assay. BJ-2302 effectively suppressed MDA-MB-231 cell invasion (Matrigel invasion assay) and metastasis (chorioallantoic membrane assay xenografted with MDA-MB-231-luc2-tdTomato cancer cells). Unlike Z-FL-COCHO (potent CTSS inhibitor), BJ-2302 did not induce any cytotoxicity in MCF-10A normal breast epithelial cells. Additionally, BJ-2302 (1 mg/kg) strongly suppressed TNBC cell proliferation in vitro and tumor growth in a xenograft mouse tumor model. The anti-metastatic and anti-tumor effects of BJ-2302 were superior to those of Z-FL-COCHO (1 mg/kg) or batimastat (30 mg/kg), a pan-MMP inhibitor. In summary, inhibition of Src kinase suppressed TNBC tumor growth and metastasis, and Src inhibitors such as BJ-2302 may constitute a novel therapeutic tool to treat breast cancer that expresses high levels of CTSS and MMP-9.

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Trastuzumab and survival of patients with metastatic breast cancer

Cited by 24 publications

References 27 publications

miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R

miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R

2′‐Hydroxyflavanone inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP76

Down-regulation of cathepsin S and matrix metalloproteinase-9 via Src, a non-receptor tyrosine kinase, suppresses triple-negative breast cancer growth and metastasis

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