Stone Alexandra, Lin Kevin M, Ghelani Ghanshyam H, Patel Sanik, Benjamin Sam, Graziano Stephen, Kotula Leszek
Department of Urology, SUNY Upstate Medical University, 750 East Adams Str., Syracuse, NY 13010, USA.
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Str., Syracuse, NY 13210, USA.
Cancers (Basel). 2023 Nov 30;15(23):5664. doi: 10.3390/cancers15235664.
To assess AR's role in TNBC treatment, various existing and completed clinical trials targeting AR or co-targeting AR with other pertinent signaling molecules were analyzed. Cyclin-dependent kinase 4/6 (CDK4/6), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17 lyase), and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were some of the most prevalent biomarkers used in combination therapy with AR inhibitors in these trials. Studying how AR functions in tandem with these molecules can have increasing breakthroughs in the treatment options for TNBC. Previous studies have been largely unsuccessful in utilizing AR as the sole drug target for systemic targeted treatment in TNBC. However, there is a lack of other commonly used drug target biomarkers in the treatment of this disease, as well. Thus, analyzing the clinical benefit rate (CBR) within clinical trials that use combination therapy can prove to be imperative to the progression of improving treatment options and prognoses.
为评估雄激素受体(AR)在三阴性乳腺癌(TNBC)治疗中的作用,我们分析了各种针对AR或与其他相关信号分子共同靶向AR的现有及已完成的临床试验。细胞周期蛋白依赖性激酶4/6(CDK4/6)、细胞色素P450 17α-羟化酶/17,20-裂解酶(CYP17裂解酶)以及磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路是这些试验中与AR抑制剂联合治疗时最常用的一些生物标志物。研究AR如何与这些分子协同发挥作用,有望在TNBC的治疗选择上取得更多突破。以往的研究在将AR作为TNBC全身靶向治疗的唯一药物靶点方面大多未取得成功。然而,在这种疾病的治疗中,也缺乏其他常用的药物靶点生物标志物。因此,分析使用联合治疗的临床试验中的临床受益率(CBR)对于改善治疗选择和预后的进展至关重要。