去势抵抗性前列腺癌中的Wnt信号传导与治疗抵抗性
Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.
作者信息
Kishore Chandra, Zi Xiaolin
机构信息
Department of Urology, University of California, Irvine, 101 The City Drive South, Rt.81 Bldg.55 Rm.204, Orange, CA 92868, USA.
Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92868, USA.
出版信息
Curr Pharmacol Rep. 2023 Oct;9(5):261-274. doi: 10.1007/s40495-023-00333-z. Epub 2023 Sep 19.
PURPOSE OF REVIEW
Castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer (PCa) due to the development of resistance to androgen deprivation therapy and anti-androgens. Here, we review the emerging role of Wnt signaling in therapeutic resistance of CRPC.
RECENT FINDINGS
Convincing evidence have accumulated that Wnt signaling is aberrantly activated through genomic alterations and autocrine and paracrine augmentations. Wnt signaling plays a critical role in a subset of CRPC and in resistance to anti-androgen therapies. Wnt signaling navigates CRPC through PCa heterogeneity, neuroendocrine differentiation, DNA repair, PCa stem cell maintenance, epithelial-mesenchymal-transition and metastasis, and immune evasion.
SUMMARY
Components of Wnt signaling can be harnessed for inhibiting PCa growth and metastasis and for developing novel therapeutic strategies to manage metastatic CRPC. There are many Wnt pathway-based potential drugs in different stages of pre-clinical development and clinical trials but so far, no Wnt signaling-specific drug has been approved by FDA for clinical use in CRPC.
综述目的
去势抵抗性前列腺癌（CRPC）是前列腺癌（PCa）的一种致命形式，这是由于对雄激素剥夺疗法和抗雄激素药物产生了耐药性。在此，我们综述Wnt信号通路在CRPC治疗耐药中的新作用。
最新发现
越来越多的确凿证据表明，Wnt信号通路通过基因组改变以及自分泌和旁分泌增强而被异常激活。Wnt信号通路在一部分CRPC以及抗雄激素治疗耐药中起关键作用。Wnt信号通路通过PCa异质性、神经内分泌分化、DNA修复、PCa干细胞维持、上皮-间质转化和转移以及免疫逃逸来调控CRPC。
总结
Wnt信号通路的组成部分可用于抑制PCa生长和转移，并开发新的治疗策略来治疗转移性CRPC。有许多基于Wnt通路的潜在药物正处于临床前开发和临床试验的不同阶段，但到目前为止，尚无Wnt信号通路特异性药物获得美国食品药品监督管理局（FDA）批准用于CRPC的临床治疗。
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