Circulating tumor DNA in advanced prostate cancer: transitioning from discovery to a clinically implemented test.

Circulating tumor DNA in advanced prostate cancer: transitioning from discovery to a clinically implemented test.
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晚期前列腺癌中循环肿瘤DNA:从发现过渡到临床实施的测试。

DOI:
10.1038/s41391-018-0098-x
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发表时间:
2019-05
影响因子:
4.8
通讯作者:
Attard G
Attard G
中科院分区:
医学2区
文献类型:
--
作者:
González-Billalabeitia E;Conteduca V;Wetterskog D;Jayaram A;Attard G

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转移性去势抵抗性前列腺癌(mCRPC)的基因组景观与原发性肿瘤不同,并且在肿瘤进展期间是动态的。通过常规实体瘤活检对该过程进行实时和重复表征具有挑战性。或者,含有循环肿瘤DNA(ctDNA)的循环无细胞DNA(cfDNA)可以使用最小破坏性的血液抽取从患者血浆获得,并且适合于顺序分析。ctDNA与来自转移瘤的活检的基因组序列具有高度重叠,并且具有代表多个转移瘤的优点。具有高灵敏度和特异性的技术的可用性,例如下一代测序(NGS)和数字PCR,极大地促进了cfDNA领域的发展,并使得能够在低ctDNA分数下检测基因组改变。在mCRPC中,已在ctDNA中追踪到许多临床相关的基因组改变,包括雄激素受体(AR)畸变,已证明其与新型抗雄激素治疗的不良结局相关,以及同源重组修复(HRR)基因的改变,已证明其与PARP抑制剂的应答相关。已经提出了cfDNA分析的几种临床应用,包括其作为预后工具、作为预测性生物标志物的用途,以监测肿瘤反应和鉴定新的耐药机制。迄今为止,cfDNA分析提供了有趣的结果,但迫切需要在前瞻性临床试验中证实这些发现。
The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) differs from that of the primary tumor and is dynamic during tumor progression. The real-time and repeated characterization of this process via conventional solid tumor biopsies is challenging. Alternatively, circulating cell-free DNA (cfDNA) containing circulating tumor DNA (ctDNA) can be obtained from patient plasma using minimally disruptive blood draws and is amenable to sequential analysis. ctDNA has high overlap with the genomic sequences of biopsies from metastases and has the advantage of being representative of multiple metastases. The availability of techniques with high sensitivity and specificity, such as next-generation sequencing (NGS) and digital PCR, has greatly contributed to the development of the cfDNA field and enabled the detection of genomic alterations at low ctDNA fractions. In mCRPC, a number of clinically relevant genomic alterations have been tracked in ctDNA, including androgen receptor (AR) aberrations, which have been shown to be associated with an adverse outcome to novel antiandrogen therapies, and alterations in homologous recombination repair (HRR) genes, which have been associated with a response to PARP inhibitors. Several clinical applications have been proposed for cfDNA analysis, including its use as a prognostic tool, as a predictive biomarker, to monitor tumor response and to identify novel mechanisms of resistance. To date, the cfDNA analysis has provided interesting results, but there is an urgent need for these findings to be confirmed in prospective clinical trials.
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