Triple-Negative Breast Cancer and the Potential for Targeted Therapy

Jhan, Jing Ru; Andrechek, Eran R.

doi:10.2217/pgs-2017-0117

Cited by 166 publications

(140 citation statements)

References 99 publications

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“…Targeted radioimmunoimaging with monoclonal antibody has been considered a successful imaging for many kinds of cancer . Radiolabelled 125 I‐antiTLR5 mAb may provide a method for visualizing TLR5 expression in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Targeted radioimmunoimaging with monoclonal antibody has been considered a successful imaging for many kinds of cancer. 10 Radiolabelled 125 I-antiTLR5 mAb may provide a method for visualizing TLR5 expression in vivo. Our data suggested that 125 I-antiTLR5 mAb could be used in these TNBC tumour models, which is more clinically relevant.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, many reports showed that innate molecules were participated in tumour developments and prognosis, such as CCAT2 (a kind of long non‐coding RNA, metastasis and prognosis) and three miRNAs (potential prognostic biomarker in patients with bladder cancer) . Molecular imaging developed much quickly, which showed great potential in tumours early diagnosis and treatment based on the change of physical and metabolisms . Among them, toll‐like receptors (TLRs) caught great attention.…”

Section: Introductionmentioning

confidence: 99%

“…9 Molecular imaging developed much quickly, which showed great potential in tumours early diagnosis and treatment based on the change of physical and metabolisms. 10 Among them, toll-like receptors (TLRs) caught great attention. TLRs are membrane-bound proteins, expressed originally mainly in immunocytes, such as monocyte/macrophage, vascular endothelial cells, 11 and also expressed on other kinds of cells, such as cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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TLR5 is a new reporter for triple‐negative breast cancer indicated by radioimmunoimaging and fluorescent staining

Shi

Liu

Zhao

et al. 2019

J Cellular Molecular Medi

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Triple‐negative breast cancer (TNBC) is a highly aggressive tumour that lacks marker for targeted diagnosis. Recently, it was reported that toll‐like receptor 5 (TLR5) was associated with some kind of tumours, especially in TNBC, but whether it could be used as a non‐invasive monitoring target is not fully understood. Here, we established TLR5− 4T1 cell line with lentivirus‐shRNA‐TLR5 knock‐down transfection (with tag GFP, green fluorescent protein, TLR5− 4T1) and control TLR5+ 4T1 cell line with negative control lentivirus transfection. The effect of TLR5 down‐regulation was detected with qPCR and Western blot. 125I‐anti‐TLR5 mAb and control isotype 125I‐IgG were prepared and injected to TLR5+/− 4T1‐bearing mice models, respectively. Whole‐body phosphor‐autoradiography, fluorescence imaging and biodistribution were performed. Furthermore, ex vivo tumour TLR5 expression was proved through immunohistochemistry staining. We found that 125I‐anti‐TLR5 mAb could bind to TLR5+ 4T1 with high affinity and specificity. Whole‐body phosphor‐autoradiography after 125I‐anti‐TLR5 mAb injection showed TLR5+ 4T1 tumour images in 24 hours, more clearly in 48 hours. Radioactivities in tumour tissues were positively related with TLR5 expression. Biodistribution assay showed that 125I‐anti‐TLR5 mAb was mainly metabolized through the liver and kidney, and 125I‐anti‐TLR5 mAb was much more accumulated in TLR5+ 4T1 tumour than TLR5− 4T1. In vivo fluorescence imaging successfully showed tumour tissues clearly both in TLR5+ and TLR5− 4T1 mice compared with lentivirus untreated 4T1 tumour. Immunohistochemistry staining showed that TLR5 expression in tumours was indeed down‐regulated in TLR5− 4T1 mice. Our results indicated that 125I‐antiTLR5 mAb was an ideal agent for non‐invasive imaging of TLR5+ tumours; TLR5 may be as a novel molecular target for TNBC non‐invasive diagnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TLR5 is a new reporter for triple‐negative breast cancer indicated by radioimmunoimaging and fluorescent staining

Shi

Liu

Zhao

et al. 2019

J Cellular Molecular Medi

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“…Despite improved treatment options using therapeutic monoclonal antibodies against HER2, the acquisition of drug resistance remains a major problem and could lead to tumour recurrence . For triple negative carcinomas, no targeted therapy is available . HER2 overexpression in human breast cancer indicates a risk of recurrence independent of whether the axillary node is positive or negative for micrometastases .…”

Section: Introductionmentioning

confidence: 99%

Dasatinib inhibition of cSRC prevents the migration and metastasis of canine mammary cancer cells with enhanced Wnt and HER signalling

Timmermans-Sprang

Mestemaker

Steenlage

et al. 2019

Vet Comparative Oncology

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Human epidermal growth factor 2 (HER2) overexpression leads to aggressive mammary tumour growth. Although the prognosis of HER2+ tumours in humans is greatly improved using biologicals, therapy resistance, which may be caused by increased phosphatidyl‐3‐kinase (PI3K), rous sarcoma proto‐oncogene (cSRC) or wingless‐type MMTV integration site family (Wnt) activity, is a major concern. A recent analysis of 12 canine mammary cell lines showed an association between HER2/3 overexpression and phosphatase and tensin homologue (PTEN) deletion with elevated Wnt‐signalling. Wnt‐activity appeared to be insensitive to phosphatidyl‐3‐kinase (PI3K) inhibitors but sensitive to Src‐I1. We hypothesized that Wnt activation, was caused by HER2/3‐activated cSRC activation. The role of HER2/3 on Wnt signalling was investigated by silencing HER2/3 expression using specific small interfering RNA (siRNAs). Next, the effect of an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor on Wnt activity and migration was investigated and compared to other tyrosine kinase inhibitors (TKIs) of related signalling pathways. Finally, two TKIs, a cSRC and a PI3K inhibitor, were investigated in a zebrafish xenograft model. Silencing of HER1‐3 did not inhibit the intrinsic high Wnt activity, whereas the HER kinase inhibitor afatinib showed enhanced Wnt activity. The strongest inhibition of Wnt activity and cell viability and migration was shown by cSRC inhibitors, which also showed strong inhibition of cell viability and metastasis in a zebrafish xenograft model. HER2/3 overexpression or HER2/3‐induced cSRC activation is not the cause of enhanced Wnt activity. However, inhibition of cSRC resulted in a strong inhibition of Wnt activity and cell migration and metastasis. Further studies are needed to unravel the mechanism of cSRC activation and cSRC inhibition to restore sensitivity to HER‐inhibitors in HER2/3‐positive breast cancer.

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Breast Cancer

2022

Fundamentals of Cancer Detection, Treatment, and Prevention

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Triple-Negative Breast Cancer and the Potential for Targeted Therapy

Cited by 166 publications

References 99 publications

TLR5 is a new reporter for triple‐negative breast cancer indicated by radioimmunoimaging and fluorescent staining

TLR5 is a new reporter for triple‐negative breast cancer indicated by radioimmunoimaging and fluorescent staining

Dasatinib inhibition of cSRC prevents the migration and metastasis of canine mammary cancer cells with enhanced Wnt and HER signalling

Breast Cancer

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