斑点型痘病毒蛋白对前列腺癌分层治疗的探讨

Role of SPOP in Stratified Treatment of Prostate Cancer

前列腺癌(prostate cancer,PCa)已经成为男性第二大常见癌症,并且随着人口老龄化的不断发展,PCa的发病率和死亡率也呈现上升的趋势,其发生发展的机制也较为复杂。雄激素受体(androgen receptor,AR)信号通路的过度激活不仅促进去势抵抗性前列腺癌(castration-resistance PCa,CRPC)的发生,还对耐药性的产生起了关键作用。目前的治疗手段较为有限且伴随较多的不良反应,因此随着精准靶向治疗的不断发展,需要寻找新的治疗方案来提高疗效。已有大量研究证明,E3泛素连接酶斑点型痘病毒蛋白(speckle-type POZ protein,SPOP)与AR存在密切的相互作用关系,从而对PCa的发生发展起重要作用。因此本文将结合近年的研究论文,阐述SPOP的基本结构与功能,总结SPOP突变对PCa的影响,并从SPOP出发探讨对PCa进行分层治疗的可能性。SPOP发生突变后,可显著影响AR信号相关的通路、DNA损伤应答、免疫应答等的正常生理功能,产生不同的病理状况;而在SPOP野生型的状况下,也会发生其他基因融合事件,致应激反应蛋白失衡等病理状况,进而诱导PCa的发生发展。因此,在治疗早期对PCa患者进行基因检测,根据分子分型确定不同的个性化分层治疗方案,这可能对改善PCa的预后状况产生有利影响。

Prostate cancer(PCa)has been the second most common cancer in men with the continuous development of the aging population,the increasing incidence and mortality rate of PCa,and complex occurrence and development mechanism of PCa.The overactivation of AR signaling pathway not only promotes the occurrence of castration-resistance PCa(CPRC),but also plays a key role in the drug resistance of PCa.Current strategies of PCa treatment are relatively limited and accompanied with several serious side-effects.Therefore,the continuous development of targeted therapy,we need to find new treatments to improve the efficacy.Numerous studies have demonstrated that the abnormal function of E3 ubiquitin ligase adaptor,speckle-type POZ protein(SPOP)has a close relationship with the occurrence and progression of PCa.Herein,this review will combine recent researches to describe the basic structure and function of SPOP,summarize the effect of SPOP on PCa,and explore the possibility of stratified treatment for PCa patients with SPOP mutations or not.For example,PCa patients with SPOP mutation can evidently enhance AR signal pathway,disrupt DNA damage response and immune response,leading to occurrence and progression of PCa.While,in the case of PCa patients with SPOP wildtype,can also occur the gene fusion,leading to imbalance of stress response protein,which may induce the occurrence and progression of PCa.Thus,it is essential that using genetic testing of patients in the early stage of treatment,which may indicate the stratified treatment for PCa patients,thus improving the prognosis of PCa efficiently.