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雄激素受体:不同乳腺癌亚型中的结构、信号、功能及潜在药物研发生物标志物。

Androgen receptor: Structure, signaling, function and potential drug discovery biomarker in different breast cancer subtypes.

机构信息

Institute of Science, Nirma University, Ahmedabad, Gujarat 382481, India.

Division of Biological & Life Sciences, School of Arts & Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad, Gujarat 380009, India.

出版信息

Life Sci. 2024 Jul 1;348:122697. doi: 10.1016/j.lfs.2024.122697. Epub 2024 May 6.

Abstract

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy worldwide. >70 % of AR expression in primary and metastatic breast tumors has been observed which suggests that AR may be a new marker and a potential therapeutic target among AR-positive BC patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. Downstream signaling of AR might also affect many clinically important pathways that are emerging as clinical targets in BC. AR exhibits different behaviors depending on the breast cancer molecular subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since AR positivity's prognostic and predictive value remains uncertain, it is difficult to identify and stratify patients who would benefit from AR-targeted therapies alone. Thus, the need of the hour is to target the androgen receptor as a monotherapy or in combination with other conventional therapies which has proven to be an effective clinical strategy for the treatment of prostate cancer patients, and these therapeutic strategies are increasingly being investigated in breast cancer. Therefore, in this manuscript, we review the role of AR in various cellular processes that promote tumorigenesis and aggressiveness, in different subtypes of breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of breast cancer.

摘要

雄激素受体 (AR) 在乳腺癌 (BC) 的发病机制中逐渐成为一个重要因素,BC 是全球最常见的恶性肿瘤。在原发性和转移性乳腺癌肿瘤中观察到 >70%的 AR 表达,这表明 AR 可能是 AR 阳性乳腺癌患者的新标志物和潜在治疗靶点。对 AR 阳性乳腺癌的生物学研究表明,AR 可能与包括关键分子和受体在内的几个重要信号通路发生交叉对话。AR 的下游信号也可能影响许多临床上重要的通路,这些通路正成为 BC 的临床靶点。AR 根据乳腺癌的分子亚型表现出不同的行为。使用已经获得 FDA 批准用于前列腺癌 (PC) 的 AR 靶向药物进行的初步临床研究,为 AR 阳性乳腺癌患者带来了有希望的结果。然而,由于 AR 阳性的预后和预测价值仍不确定,因此难以确定和分层仅受益于 AR 靶向治疗的患者。因此,当务之急是将雄激素受体作为单一疗法或与其他常规疗法联合靶向治疗,这已被证明是治疗前列腺癌患者的有效临床策略,并且这些治疗策略在乳腺癌中越来越受到研究。因此,在本文中,我们综述了 AR 在促进肿瘤发生和侵袭性的各种细胞过程中的作用,以及它在不同亚型的乳腺癌中的作用,并讨论了针对 AR 的现有努力,以更有效地治疗和预防乳腺癌。

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