多西紫杉醇
前列腺癌
医学
雄激素剥夺疗法
肿瘤科
内科学
癌症
新辅助治疗
转录组
基因组学
生物
乳腺癌
基因
遗传学
基因组
基因表达
作者
Himisha Beltran,Alexander W. Wyatt,Edmund C.P. Chedgy,Adam Donoghue,Matti Annala,Evan W. Warner,Kevin Beja,Michael Sigouros,Fan Mo,Ladan Fazli,Colin C. Collins,James A. Eastham,Michael J. Morris,Mary‐Ellen Taplin,Andrea Sboner,Susan Halabi,Martin Gleave
标识
DOI:10.1158/1078-0432.ccr-17-1034
摘要
Abstract Purpose: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify potential biomarkers. Experimental Design: We evaluated baseline clinical data, needle biopsies, and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline-targeted DNA sequencing (n = 72 genes), and expression profiling using NanoString platform (n = 163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance. Results: Three of 52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n = 32), TP53 mutation or deletion (n = 11), PTEN deletion (n = 6), FOXA1 (n = 6), and SPOP (n = 4) mutation, with no significant enrichment in posttreated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was upregulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes. Conclusions: These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise posttreatment provides new insight into potential early markers of resistance. Clin Cancer Res; 23(22); 6802–11. ©2017 AACR.
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