Management of ER positive metastatic breast cancer

McAndrew, Nicholas P.; Finn, Richard S.

doi:10.1053/j.seminoncol.2020.07.005

Cited by 28 publications

(25 citation statements)

References 69 publications

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“…CDK4/6 inhibitors (palbociclib and its analogues) have been approved for the treatment of hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer, with the aim to block the self-renewal of CSCs. Clinical trials demonstrated their effectiveness when paired with standard therapies, doubling the median progressionfree survival [222,223]. Importantly, due to their significant efficacy, CDK4/6 inhibitors are now recommended in the clinical practice, in the first-line or second-line setting in women with HR+, HER2-breast cancer, in combination with hormonal or targeted therapies [224].…”

Section: Figurementioning

confidence: 99%

Cancer Stem Cells—Key Players in Tumor Relapse

Marzagalli

Fontana

Raimondi

et al. 2021

Cancers

102

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Tumor relapse and treatment failure are unfortunately common events for cancer patients, thus often rendering cancer an uncurable disease. Cancer stem cells (CSCs) are a subset of cancer cells endowed with tumor-initiating and self-renewal capacity, as well as with high adaptive abilities. Altogether, these features contribute to CSC survival after one or multiple therapeutic approaches, thus leading to treatment failure and tumor progression/relapse. Thus, elucidating the molecular mechanisms associated with stemness-driven resistance is crucial for the development of more effective drugs and durable responses. This review will highlight the mechanisms exploited by CSCs to overcome different therapeutic strategies, from chemo- and radiotherapies to targeted therapies and immunotherapies, shedding light on their plasticity as an insidious trait responsible for their adaptation/escape. Finally, novel CSC-specific approaches will be described, providing evidence of their preclinical and clinical applications.

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Section: Figurementioning

confidence: 99%

Cancer Stem Cells—Key Players in Tumor Relapse

Marzagalli

Fontana

Raimondi

et al. 2021

Cancers

102

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“…In recent years, many new classes of antitumour compounds with a significant effect on the signalling pathways in tumour cells have been developed [1][2][3][4][5][6]. Along with the new classes, antihormonal drugs-SERMs (selective oestrogen receptor modulators) and SERDs (selective oestrogen receptor degraders)-remain highly relevant as an antitumour therapy [7][8][9]. Hormone therapy [10][11][12][13][14] is one of the most common types of treatment of hormone-dependent tumours including breast cancer, ovarian cancer, endometrial and prostate tumours.…”

Section: Introductionmentioning

confidence: 99%

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

et al. 2021

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Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

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“…Tamoxifen (TAM) is a classic ER-positive breast cancer treated drugs [3]. Unfortunately, it usually develops into TAM-resistance.…”

Section: Introductionmentioning

confidence: 99%

Curcumol Inhibit Breast Cancer Growth Via NCL/ERα36 And PI3K/AKT Pathway

Wei

Wang

Dou

et al. 2021

Preprint

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Purpose: This study is to investigate the effect and mechanism of curcumol on ERα36 positive breast cancer cells, and the relationship between curcumol’s target protein nucleolin (NCL) and ERα36. Methods: The anti-tumor effect of curcumol were quantified via MTT assay, colony formation and cycle arrest respectively. The expression of ERα36, NCL and the proteins involved in PI3K/AKT signaling were evaluated by western blotting. The interaction between two proteins were detected using co-immunoprecipitation (Co-IP) and immunofluorescence assay. Mouse xenograft model was established to verify the role of ERα36 in breast cancer cells and curcumol’s effect on ERα36 positive cancer cells. Results: Curcumol inhibited the cell growth, caused cell cycle arrest, decreased cell cycle related-proteins and inactivated PI3K/AKT pathway in ERα36 positive breast cancer cells. There is a positive correlation between NCL and ERα36 in breast cancer cells. In addition, ERα36 bound to NCL, the two proteins were distributed in the nucleus, cytoplasm and on the plasma membrane, where their expression were obviously decreased by curcumol. Moreover, NCL silenced by NCL siRNA blocked the cell cycle progress and inhibited the activation of PI3K/AKT in MDA-MB-231 cells, while overexpressed ERα36 increased the expression of NCL, promoted cell cycle progress and enhanced the activity of PI3K/AKT in MCF-7 cells. NCL knockdown or ERα36 overexpressed all attenuated the effect of curcumol on breast cancer cells. Conclusion: Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivated PI3K/AKT pathway.

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Management of ER positive metastatic breast cancer

Cited by 28 publications

References 69 publications

Cancer Stem Cells—Key Players in Tumor Relapse

Cancer Stem Cells—Key Players in Tumor Relapse

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance

Curcumol Inhibit Breast Cancer Growth Via NCL/ERα36 And PI3K/AKT Pathway

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