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

González-Billalabeitia, E; Conteduca, V; Wetterskog, D; Jayaram, A; Attard, G; (2019) Circulating tumor DNA in advanced prostate cancer: transitioning from discovery to a clinically implemented test. Prostate Cancer and Prostatic Diseases , 22 pp. 195-205. 10.1038/s41391-018-0098-x. Green open access

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Abstract

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.

Type: Article
Title: Circulating tumor DNA in advanced prostate cancer: transitioning from discovery to a clinically implemented test
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41391-018-0098-x
Publisher version: https://doi.org/10.1038/s41391-018-0098-x
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10065655
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