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JAMA Oncology:治疗前列腺癌——看基因选药

来源:生物谷 2015-06-15 11:48

                                                                   

2015年6月15日讯 /生物谷BIOON/ --在一项小型临床研究中,来自约翰霍普金斯基梅尔癌症中心和詹姆斯布坎南布拉迪泌尿学研究所的科学家们发现患有晚期前列腺癌同时携带雄激素受体剪切突变7(AR-V7)的男性患者对传统化疗方法的药物应答情况与不携带突变的前列腺癌患者一样好。近日,相关研究结果发表在国际学术期刊JAMA Oncology。
 
研究人员指出,这项研究发现可能对于携带AR-V7突变的病人具有非常重要的意义,他们的研究显示携带AR-V7基因突变的病人通常不会对激素类治疗药物阿比特龙和恩杂鲁胺产生药物应答,但携带这一突变对于使用传统化疗药物进行治疗来说并没有任何不利之处。
 
这项研究共有37名前列腺癌患者参与,他们都接受了多西他奇和卡巴他赛两种化疗药物中的一种进行治疗,其中有17名携带AR-V7突变的晚期前列腺癌病人。结果在进行了化疗治疗后,与不携带该基因突变的病人相比,携带突变的病人并没有在前列腺癌特异性抗原(PSA)表达水平,癌症进展所需时间以及总体生存率上存在显著性差异。并且这17人中有7名患者的前列腺特异性抗原(PSA)的水平下降了50%。
 
总得来说,如果这项研究结果能够在更大的临床实验中得到验证,将表明AR-V7基因突变的出现或可作为一种生物标记物,可帮助前列腺癌病人做出更合理的治疗决策,因此这项研究对于前列腺癌的合理治疗,提高治疗效果具有重要意义。(生物谷Bioon.com)
 
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Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer
 
Emmanuel S. Antonarakis, MD1; Changxue Lu, PhD2; Brandon Luber, ScM1; Hao Wang, PhD1; Yan Chen, PhD2; Mary Nakazawa, MHS2; Rosa Nadal, MD1; Channing J. Paller, MD1; Samuel R. Denmeade, MD1; Michael A. Carducci, MD1; Mario A. Eisenberger, MD1; Jun Luo, PhD
 
Importance  We previously showed that detection of androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) from men with castration-resistant prostate cancer (CRPC) was associated with primary resistance to enzalutamide and abiraterone therapy, but the relevance of AR-V7 status in the context of chemotherapy is unknown.
 
Objective  To investigate whether AR-V7-positive patients would retain sensitivity to taxane chemotherapy and whether AR-V7 status would have a differential impact on taxane-treated men compared with enzalutamide- or abiraterone-treated men.
 
Design, Setting, and Participants  We examined CTCs for AR-V7 mRNA using a reverse-transcription polymerase chain reaction assay. From January 2013 to July 2014, we prospectively enrolled patients with metastatic CRPC initiating taxane chemotherapy (docetaxel or cabazitaxel) at a single academic institution (Johns Hopkins). Our prespecified statistical plan required a sample size of 36 taxane-treated men.
 
Main Outcomes and Measures  We evaluated associations between AR-V7 status and prostate-specific antigen (PSA) response rates, PSA progression-free survival (PSA PFS), and clinical and/or radiographic progression-free survival (PFS). After incorporating updated data from our prior study of 62 patients treated with enzalutamide or abiraterone, we also investigated the interaction between AR-V7 status (positive or negative) and treatment type (taxane vs enzalutamide or abiraterone).
 
Results  Of 37 taxane-treated patients enrolled, 17 (46%) had detectable AR-V7 in CTCs. Prostate-specific antigen responses were achieved in both AR-V7-positive and AR-V7-negative men (41% vs 65%; P?=?.19). Similarly, PSA PFS (hazard ratio [HR], 1.7, 95% CI, 0.6-5.0; P?=?.32) and PFS (HR, 2.7, 95% CI, 0.8-8.8; P?=?.11) were comparable in AR-V7-positive and AR-V7-negative patients. A significant interaction was observed between AR-V7 status and treatment type (P?<?.001). Clinical outcomes were superior with taxanes compared with enzalutamide or abiraterone therapy in AR-V7-positive men, whereas outcomes did not differ by treatment type in AR-V7-negative men. In AR-V7-positive patients, PSA responses were higher in taxane-treated vs enzalutamide- or abiraterone-treated men (41% vs 0%; P?<?.001), and PSA PFS and PFS were significantly longer in taxane-treated men (HR, 0.19 [95% CI, 0.07-0.52] for PSA PFS, P?=?.001; HR, 0.21 [95% CI, 0.07-0.59] for PFS, P?=?.003).
 
Conclusions and Relevance  Detection of AR-V7 in CTCs from men with metastatic CRPC is not associated with primary resistance to taxane chemotherapy. In AR-V7-positive men, taxanes appear to be more efficacious than enzalutamide or abiraterone therapy, whereas in AR-V7-negative men, taxanes and enzalutamide or abiraterone may have comparable efficacy. Circulating tumor cell-based AR-V7 detection may serve as a treatment selection biomarker in CRPC.
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