前列腺癌是男性中第二常见的癌症，占全球癌症相关死亡的五分之一。尽管有有效的前列腺癌疗法，但如果不能通过根治性局部治疗治愈，进展为耐药性转移性前列腺癌是不可避免的。因此，迫切需要新的药物和治疗方案来克服耐药性。我们最近发表的研究表明，针对内体回收途径（一种将内化的细胞表面蛋白回收回质膜的膜运输途径）可能是下调临床相关细胞表面蛋白并有可能克服耐药性的一种新方法。对用内体再循环抑制剂处理的乳腺癌细胞进行的反相蛋白阵列 (RPPA) 分析发现，雄激素受体 (AR) 是最下调的蛋白质之一。我们证实内体再循环抑制剂也下调前列腺癌细胞中的 AR，并表明这种情况发生在转录水平。我们还发现内体再循环抑制剂与恩杂鲁胺（一种前列腺癌的标准治疗方法）具有协同作用。我们的数据表明，将回收抑制剂与激素受体拮抗剂相结合可以增强其功效并减少耐药性的出现。© 2023。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下子公司）的独家许可。

Prostate cancer is the second most frequent cancer diagnosed in men, and accounts for one-fifth of cancer associated deaths worldwide. Despite the availability of effective prostate cancer therapies, if it is not cured by radical local treatment, progression to drug resistant metastatic prostate cancer is inevitable. Therefore, new drugs and treatment regimens are urgently required to overcome resistance. We have recently published research demonstrating that targeting the endosomal recycling pathway, a membrane transport pathway that recycles internalised cell surface proteins back to the plasma membrane, may be a novel means to downregulate clinically relevant cell surface proteins and potentially overcome drug resistance. A reverse phase protein array (RPPA) assay of breast cancer cells treated with an endosomal recycling inhibitor identified the androgen receptor (AR) as one of the top downregulated proteins. We confirmed that endosomal recycling inhibitors also downregulated AR in prostate cancer cells and show that this occurs at the transcriptional level. We also found that endosomal recycling inhibitors synergise with enzalutamide, a standard-of-care therapy for prostate cancer. Our data suggest that combining recycling inhibitors with hormone receptor antagonists may enhance their efficacy and reduce the emergence of drug resistance.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.