The NF-κB Pathway Promotes Tamoxifen Tolerance and Disease Recurrence in Estrogen Receptor–Positive Breast Cancers

Kastrati, Irida; Joosten, Stacey E. P.; Semina, Svetlana E.; Alejo, Luis H.; Brovkovych, Svitlana D.; Stender, Joshua D.; Horlings, Hugo M.; Kok, Marleen; Alarid, Elaine T.; Greene, Geoffrey L.; Linn, Sabine C.; Zwart, Wilbert; Frasor, Jonna

doi:10.1158/1541-7786.mcr-19-1082

Cited by 38 publications

(29 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The activity of NF‐κB is suppressed by COUP-TFII and decreased COUP-TFII expression results in an endocrine-resistant phenotype ( 107 ). The NF‐κB signaling pathway inhibitor (ACT001) in combination with tamoxifen hinders the proliferation of tamoxifen-resistant cells ( 108 ), hence NF-κB inhibition plays a promising approach to prevent tamoxifen resistance ( 109 ).…”

Section: Endocrine Resistancementioning

confidence: 99%

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Belachew

Sewasew

2021

Front. Endocrinol.

View full text Add to dashboard Cite

The estrogen receptor is a vital receptor for therapeutic targets in estrogen receptor-positive breast cancer. The main strategy for the treatment of estrogen receptor-positive breast cancers is blocking the estrogen action on estrogen receptors by endocrine therapy but this can be restricted via endocrine resistance. Endocrine resistance occurs due to both de novo and acquired resistance. This review focuses on the mechanisms of the ligand-dependent and ligand-independent pathways and other coregulators, which are responsible for endocrine resistance. It concludes that combinatorial drugs that target different signaling pathways and coregulatory proteins together with endocrine therapy could be a novel therapeutic modality to stop endocrine resistance.

show abstract

Section: Endocrine Resistancementioning

confidence: 99%

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Belachew

Sewasew

2021

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Kastrati at al. ( 35 ) reported that NF-κB pathway promotes tamoxifen tolerance and disease metastasis in estrogen receptor-positive BRCAs.…”

Section: Chemoresistance Mechanisms In Brcamentioning

confidence: 99%

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies

et al. 2021

View full text Add to dashboard Cite

Breast cancer is the most common malignant tumor in females worldwide. Chemotherapy is the standard breast cancer treatment; however, chemoresistance is often seen in patients with metastatic breast cancer. Owing to high heterogeneity, the mechanisms of breast cancer chemoresistance and metastasis have not been fully investigated. The possible molecular mechanisms of chemoresistance in breast cancer include efflux transporters, signaling pathways, non-coding RNAs, and cancer stem cells. However, to overcome this hurdle, the use of novel clinical strategies such as drug carriers, immunotherapy, and autophagy regulation, are being investigated. The goal of this review is to summarize the current data about the molecular mechanisms of breast cancer chemoresistance and the novel clinical strategies; thus, providing a useful clinical tool to explore optimal treatment for breast cancer.

show abstract

“…It is tempting to speculate that the reduced recurrence and breast cancer-related mortality in patients who receive tamoxifen for 10 years compared to only 5 years (Davies et al, 2013;Gray et al, 2013) is due to a sustained EMP-induced dormant state. Indeed, evidence has accumulated that endocrine therapy induces EMT signatures in ER+ BC (Creighton et al, 2009;Kastrati et al, 2020;Sflomos et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening

Patrik

Yueyun

Stibolt

et al. 2021

Preprint

View full text Add to dashboard Cite

Estrogen receptor α-positive (ER+) breast cancers (BCs) represent more than 70% of all breast cancers and pose a particular clinical challenge because they recur up to decades after initial diagnosis and treatment. The mechanisms governing tumor cell dormancy and latent disease remain elusive due to a lack of adequate models. Here, we compare tumor progression of ER+ and triple-negative (TN) BC subtypes with a clinically relevant mouse intraductal xenografting approach (MIND). Both ER+ and TN BC cells disseminate already during the in situstage. However, TN disseminated tumor cells (DTCs) proliferate at the same rate as cells at the primary site and give rise to macro-metastases. ER+ DTCs have low proliferative indices, form only micro-metastases and lose epithelial characteristics. Expression of CDH1 is decreased whereas the mesenchymal marker VIM and the transcription factors, ZEB1/ZEB2, which control epithelial-mesenchymal plasticity (EMP) are increased. EMP is not detected earlier during ER+ BC development and not required for invasion or metastasis. In vivo, forced transition to the epithelial state through ectopic E-cadherin expression overcomes dormancy with increased growth of lung metastases. We conclude that EMP is essential for the generation of a dormant cell state and the development of latent disease. Targeting exit from EMP is of therapeutic potential.

show abstract

The NF-κB Pathway Promotes Tamoxifen Tolerance and Disease Recurrence in Estrogen Receptor–Positive Breast Cancers

Cited by 38 publications

References 50 publications

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Molecular Mechanisms of Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies

Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening

Contact Info

Product

Resources

About