4.5 Article

Regulation of aromatase expression: Potential therapeutic insight into breast cancer treatment

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2021.111321

关键词

Aromatase; Estrogen signaling; Transcriptional and post-translational regula-tion; Aromatase inhibition; Breast cancer

资金

  1. Cancer Prevention and Research Institute of Texas (CPRIT) Award [RR140008]

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Estrogen signaling plays a crucial role in hormone-dependent breast cancer, with treatments involving AIs and modulators of estrogen receptors. However, the development of acquired resistance poses a serious clinical challenge in breast cancer treatment.
Estrogen signaling has been implicated in hormone-dependent breast cancer which constitutes >75% of breast cancer diagnosis and other malignancies. Aromatase, the key enzyme involved in the synthesis of estrogen, is often dysregulated in breast cancers. This has led to the administration of aromatase-inhibitors (AIs), commonly used for hormone-dependent breast cancers. Unfortunately, the increasing development of acquired resistance to the current AIs and modulators of estrogen receptors, following initial disease steadiness, has posed a serious clinical challenge in breast cancer treatment. In this review we highlight historical and recent advances on the transcriptional and post-translational regulation of aromatase in both physiological and pathological contexts. We also discuss the different drug combinations targeting various tumor promoting cell signaling pathways currently being developed and tested both in laboratory settings and in the clinic.

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