Recent development of targeted approaches for the treatment of breast cancer

Maruthanila, V L; Elancheran, R.; Kunnumakkara, Ajaikumar B.; Kabilan, S.; Kotoky, Jibon

doi:10.1007/s12282-016-0732-1

Cited by 68 publications

(31 citation statements)

References 69 publications

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“…Discovery of therapeutic targets and development of novel targeted agents has changed the landscape in the battle field against breast cancer in the past few decades [ 8 ]. A variety of master genes, including ER, human epidermal growth factor receptor-2 (HER-2), and cyclin dependent kinase (CDK)4/6 have been identified to be involved in the development and progression of BC [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

FoxM1 is a promising candidate target in the treatment of breast cancer

Zeng

Liang

et al. 2017

Oncotarget

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Forkhead box protein M1(FoxM1) is a member of forkhead superfamily transcription factors. Emerging evidences have progressively contributed to our understanding on a central role of FoxM1 in human cancers. However, perspectives on the function of FoxM1 in breast cancer (BC) remain conflicting, and mostly were from basic research. Here, we explored the expression profile and prognostic values of FoxM1 based on analysis of pooled clinical datasets derived from online accessible databases, including ONCOMINE, Breast Cancer Gene-Expression Miner v4.0, and Kaplan-Meier plotter. It was found that, FoxM1 mRNA expression was significantly higher in breast tumor versus normal control. FoxM1expression profile presented a distinct pattern in different molecular subtypes of BC patients. Higher expression of FoxM1 was correlated to low mRNA expression of estrogen receptor 1 (ESR1), erb-B2 receptor tyrosine kinase 2 (ERBB2), and was inversely associated with the expression of classical luminal regulators forkhead box protein A1 (FoxA1) and GATA binding protein 3 (GATA3). Elevated FoxM1 expression predicted shorter distance metastasis free survival (DMFS) in BC patients, particularly with estrogen receptor (ER) positive and Luminal A, Luminal B subtypes of BC. More interestingly, elevated FoxM1 expression predicted poor survival in breast cancer patients, especially in the ER (+), progesterone receptor (PR) (+) subgroups and BC patients received adjuvant chemotherapy only or treated with tamoxifen only. These results implied that FoxM1 is an essential prognostic factor and promising candidate target in the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

FoxM1 is a promising candidate target in the treatment of breast cancer

Zeng

Liang

et al. 2017

Oncotarget

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“…Metastasis is the primary cause of breast cancer mortality [ 19 , 20 ], and miRNAs are involved in regulating the behavior of tumor metastasis [ 21 , 22 ]. Here, we proposed a model in which TGF-β is capable of inducing tumorigenic through the reduction of miR-196a-3p, which targets NRP2, leading to its accumulation (Figure 8 ), providing novel potential targets for the treatment of metastatic breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression

Chen

Huang

Wu³

et al. 2017

Oncotarget

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Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

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“…Breast cancer, a heterogeneous disease with diversity in morphological features and histological characteristics, is the most prominent leading cause of cancer death in women all over the world 1 . Despite the development of chemotherapy options for cancer, treatment has been limited because of numerous side effects that lead to failure of treatment 2 . Therefore, to overcome these deficiencies and minimizing the side effects, recognition of safe drugs especially with natural origin is essential 3 – 5 .…”

Section: Introductionmentioning

confidence: 99%

In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell cultures and the study of their interaction mode with DNA

Jamali

Kavoosi

Safavi

et al. 2018

Sci Rep

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Oliveria decumbens is an Iranian endemic plant used extensively in traditional medicine. Recently, some studies have been performed on biological effects of Oliveria essential oil (OEO). However, to our knowledge, the anticancer activity of OEO has not been reported. Based on our GC/MS analysis, the basic ingredients of OEO are thymol, carvacrol, p-cymene and γ-terpinene. Therefore, we used OEO and its main component, thymol, to explore their effects on cell growth inhibition and anticancer activity. Despite having a limited effect on L929 normal cells, OEO/thymol induced cytotoxicity in MDA-MB231 breast cancer monolayers (2D) and to a lesser extent in MDA-MB231 spheroids (3D). Flow cytometry, caspase-3 activity assay in treated monolayers/spheroids and also fluorescence staining and DNA fragmentation in treated monolayers demonstrated apoptotic death mode. Indeed, OEO/thymol increased the Reactive Oxygen Species (ROS) level leading to mitochondrial membrane potential (MMP, ΔΨm) loss, caspase-3 activation and DNA damage caused S-phase cell cycle arrest. Furthermore, immunoblotting studies revealed the activation of intrinsic and maybe extrinsic apoptosis pathways by OEO/thymol. Additionally, in-vitro experiments, indicated that OEO/thymol interacts with DNA via minor grooves confirmed by docking method. Altogether, our reports underlined the potential of OEO to be considered as a new candidate for cancer therapy.

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Recent development of targeted approaches for the treatment of breast cancer

Cited by 68 publications

References 69 publications

FoxM1 is a promising candidate target in the treatment of breast cancer

FoxM1 is a promising candidate target in the treatment of breast cancer

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression

In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell cultures and the study of their interaction mode with DNA

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