Treatment for the endocrine resistant breast cancer: Current options and future perspectives

Liu, Chunyu; Wu, Chongsheng; Petrossian, Karineh; Huang, Tzu Ting; Tseng, Ling‐Ming; Chen, Shiuan

doi:10.1016/j.jsbmb.2017.07.001

Cited by 43 publications

(42 citation statements)

References 135 publications

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“…So far, only few diagnostic markers are well recognized in invasive BC, including expression of the two nuclear receptors (NR), the estrogen receptor (ER) and progesterone receptor (PR), and overexpression of human epidermal 2 of 14 growth factor receptor 2 (HER2). Although therapies targeting ER and HER2 (e.g., tamoxifen and trastuzumab) have been very successful, some tumors ultimately develop resistance to single or even combination therapies [4]. Thus, the identification of other biomarkers is essential for optimal and personalized BC management.…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Shao¹,

Kühn²,

Mayr

et al. 2020

IJMS

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The aim of this study was to investigate the expression of thyroid hormone receptor β1 (THRβ1) by immunohistochemistry in breast cancer (BC) tissues and to correlate the results with clinico-biological parameters. In a well-characterized cohort of 274 primary BC patients, THRβ1 was widely expressed with a predominant nuclear location, although cytoplasmic staining was also frequently observed. Both nuclear and cytoplasmic THRβ1 were correlated with high-risk BC markers such as human epidermal growth factor receptor 2 (HER2), Ki67 (also known as MKI67), prominin-1 (CD133), and N-cadherin. Overall survival analysis demonstrated that cytoplasmic THRβ1 was correlated with favourable survival (p = 0.015), whereas nuclear THRβ1 had a statistically significant correlation with poor outcome (p = 0.038). Interestingly, in our cohort, nuclear and cytoplasmic THRβ1 appeared to be independent markers either for poor (p = 0.0004) or for good (p = 0.048) prognosis, respectively. Altogether, these data indicate that the subcellular expression of THRβ1 may play an important role in oncogenesis. Moreover, the expression of nuclear THRβ1 is a negative outcome marker, which may help to identify high-risk BC subgroups.

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Section: Introductionmentioning

confidence: 99%

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Shao¹,

Kühn²,

Mayr

et al. 2020

IJMS

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show abstract

“…In recent years, both clinical observations and experimental studies have shown that the therapeutic efficacy of anticancer drugs can be altered by steroid hormones and their receptors, but the potential molecular mechanisms remain unclear. [34][35][36] In this study, using our established paclitaxel-resistant breast cancer cells, we explored whether and how IBC influenced paclitaxel resistance in breast cancer cells via the ERa-dependent pathway. First, we verified that IBC can reverse E 2 -induced paclitaxel resistance in ER+ breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Isobavachalcone sensitizes cells to E2‐induced paclitaxel resistance by down‐regulating CD44 expression in ER+ breast cancer cells

Shi

Chen²,

Chen

et al. 2018

J Cellular Molecular Medi

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Oestrogen receptor (ER) is expressed in approximately 60%‐70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER‐positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER‐negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β‐estradiol (E2)‐induced paclitaxel resistance and that E2 could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E2 could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel‐resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down‐regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel‐resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.

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“…A number of researchers have generated different cell line models with the aim of understanding the mechanisms of such AI resistance on the molecular level and developing avenues to overcome it [1][2][3][4][5]. The most attractive hypothesis is that resistance implies a selection process that involves the activation of alternative regulatory survival pathways allowing cancer to recur, although estrogen production is suppressed by AIs [6,7]. In particular, aberrant crosstalk among growth factor signaling pathways, including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), and the ER signaling converging in the activation of downstream RAF/MEK/ERK and PI3K/Akt/mTOR pathways has been shown to be crucial in driving cell survival and proliferation in many patients progressing on endocrine treatment [6,8].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, aberrant crosstalk among growth factor signaling pathways, including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), and the ER signaling converging in the activation of downstream RAF/MEK/ERK and PI3K/Akt/mTOR pathways has been shown to be crucial in driving cell survival and proliferation in many patients progressing on endocrine treatment [6,8]. Therefore, a few agents targeting these signaling pathways have been explored in current clinical trials, but results have been somewhat unsatisfactory [7], highlighting the unmet need of elucidating other dynamic changes that enable breast cancer cells to escape over the course of treatment.…”

Section: Introductionmentioning

confidence: 99%

Leptin Signaling Contributes to Aromatase Inhibitor Resistant Breast Cancer Cell Growth and Activation of Macrophages

et al. 2020

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Obesity represents a risk factor for breast cancer development and therapy resistance, but the molecular players underling these links are unclear. Here, we identify a role for the obesity-cytokine leptin in sustaining aromatase inhibitor (AI) resistant growth and progression in breast cancer. Using as experimental models MCF-7 breast cancer cells surviving long-term treatment with the AI anastrozole (AnaR) and Ana-sensitive counterparts, we found that AnaR cells expressed higher levels of leptin and its receptors (ObR) along with a constitutive activation of downstream effectors. Accordingly, leptin signaling inhibition reduced only AnaR cell growth and motility, highlighting the existence of an autocrine loop in mechanisms governing drug-resistant phenotypes. In agreement with ObR overexpression, increasing doses of leptin were able to stimulate to a greater extent growth and migration in AnaR than sensitive cells. Moreover, leptin contributed to enhanced crosstalk between AnaR cells and macrophages within the tumor microenvironment. Indeed, AnaR, through leptin secretion, modulated macrophage profiles and increased macrophage motility through CXCR4 signaling, as evidenced by RNA-sequencing, real-time PCR, and immunoblotting. Reciprocally, activated macrophages increased AnaR cell growth and motility in coculture systems. In conclusion, acquired AI resistance is accompanied by the development of a leptin-driven phenotype, highlighting the potential clinical benefit of targeting this cytokine network in hormone-resistant breast cancers, especially in obese women.

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Treatment for the endocrine resistant breast cancer: Current options and future perspectives

Cited by 43 publications

References 135 publications

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Isobavachalcone sensitizes cells to E2‐induced paclitaxel resistance by down‐regulating CD44 expression in ER+ breast cancer cells

Leptin Signaling Contributes to Aromatase Inhibitor Resistant Breast Cancer Cell Growth and Activation of Macrophages

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