Biomarkers for Predicting Abiraterone Treatment Outcome and Selecting Alternative Therapies in Castration-Resistant Prostate Cancer.
Biomarkers for Predicting Abiraterone Treatment Outcome and Selecting Alternative Therapies in Castration-Resistant Prostate Cancer.
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DOI：
10.1002/cpt.2582
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发表时间：
2022-06
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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作者：
大约三分之一的转移性去势抵抗性前列腺癌（CRPC）患者表现出原发性阿比特龙耐药。为了确定阿比特龙无应答者的替代治疗，我们使用L1000数据库进行了药物发现分析，使用了在PROMOTE试验中招募的阿比特龙应答者和无应答者之间的肿瘤活检和患者来源的异种移植（PDX）肿瘤中鉴定的差异表达基因。该方法确定了3种药物，包括拓扑异构酶II（TOP 2）抑制剂米托蒽醌、CDK 4/6抑制剂palbociclib和泛CDK抑制剂PHA-793887。这些药物显著抑制阿比特龙耐药细胞系和PDX模型的生长。此外，我们确定了所有3种药物靶向的11个基因，这些基因与PROMOTE和Stand Up To Cancer队列中的不良结局相关。该11个基因组也可能作为生物标志物，为该CRPC患者亚组选择3种替代疗法，从而促进进一步的临床研究。
Approximately one‐third of patients with metastatic castration‐resistant prostate cancer (CRPC) exhibited primary abiraterone resistance. To identify alternative treatment for abiraterone nonresponders, we performed drug discovery analyses using the L1000 database using differentially expressed genes identified in tumor biopsies and patient‐derived xenograft (PDX) tumors between abiraterone responders and nonresponders enrolled in PROMOTE trial. This approach identified 3 drugs, including topoisomerase II (TOP2) inhibitor mitoxantrone, CDK4/6 inhibitor palbociclib, and pan‐CDK inhibitor PHA‐793887. These drugs significantly suppressed the growth of abiraterone‐resistant cell lines and PDX models. Moreover, we identified 11 genes targeted by all 3 drugs that were associated with worse outcomes in both the PROMOTE and Stand Up To Cancer cohorts. This 11‐gene panel might also function as biomarkers to select the 3 alternative therapies for this subgroup of patients with CRPC, warranting further clinical investigation.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
DOI：
10.1158/1078-0432.ccr-08-2660
发表时间：
2009-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Knudsen KE;Scher HI
通讯作者：
Scher HI
影响因子：
1.6
作者：
Giatromanolaki, Alexandra;Fasoulaki, Virginia;Koukourakis, Michael I
通讯作者：
Koukourakis, Michael I
影响因子：
45.3
作者：
Millikan, Randall E.;Wen, Sijin;Logothetis, Christopher J.
通讯作者：
Logothetis, Christopher J.