PDF(Pubmed)
Abstract：
Prostate cancer is one of the most prevalent malignancies and is primarily driven by aberrant androgen receptor (AR) signaling. While AR-targeted therapies form the cornerstone of prostate cancer treatment, they often inadvertently activate compensatory pathways, leading to therapy resistance. This resistance is frequently mediated through changes in transcription factor (TF) crosstalk, reshaping gene regulatory programs and ultimately weakening treatment efficacy. Consequently, investigating TF interactions has become crucial for understanding the mechanisms driving therapy-resistant cancers. Recent evidence has highlighted the crosstalk between the glucocorticoid receptor (GR) and AR, demonstrating that GR can induce prostate cancer therapy resistance by replacing the inactivated AR, thereby becoming a driver of the disease. In addition to this oncogenic role, GR has also been shown to act as a tumor suppressor in prostate cancer. Owing to this dual role and the widespread use of glucocorticoids as adjuvant therapy, it is essential to understand GR\'s actions across different stages of prostate cancer development. In this review, we explore the current knowledge of GR in prostate cancer, with a specific focus on its crosstalk with other TFs. GR can directly and indirectly interact with a variety of TFs, and these interactions vary significantly depending on the type of prostate cancer cells. By highlighting these crosstalk interactions, we aim to provide insights that can guide the research and development of new GR-targeted therapies to mitigate its harmful effects in prostate cancer.
摘要：
前列腺癌是最常见的恶性肿瘤之一，主要由异常雄激素受体（AR）信号驱动。虽然AR靶向治疗是前列腺癌治疗的基石，它们经常无意中激活代偿途径，导致治疗抵抗。这种抗性通常是通过转录因子（TF）串扰的变化来介导的，重塑基因调控方案，最终削弱治疗效果。因此,研究TF相互作用对于理解驱动治疗耐药癌症的机制至关重要.最近的证据强调了糖皮质激素受体（GR）和AR之间的串扰，证明GR可以通过替代灭活的AR来诱导前列腺癌治疗抵抗，从而成为疾病的驱动力。除了这种致癌作用，GR也已被证明在前列腺癌中起肿瘤抑制因子的作用。由于这种双重作用以及糖皮质激素作为辅助治疗的广泛使用，了解GR在前列腺癌发展的不同阶段的作用是至关重要的。在这次审查中,我们探索了前列腺癌中GR的最新知识，特别关注其与其他TF的串扰。GR可以直接和间接地与各种TFs相互作用，这些相互作用根据前列腺癌细胞的类型而显著变化。通过突出这些串扰相互作用，我们的目标是提供可以指导研究和开发新的GR靶向疗法以减轻其在前列腺癌中的有害影响的见解。
