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

Prostate Cancer and Prostatic Diseases (2018) | Download Citation

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.

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Author notes

  1. These authors have contributed equally: Enrique González-Billalabeitia, Vincenza Conteduca

Affiliations

  1. Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, IMIB-Universidad de Murcia, Murcia, 30008, Spain

    • Enrique González-Billalabeitia
  2. Universidad Católica San Antonio de Murcia (UCAM), Murcia, 30107, Spain

    • Enrique González-Billalabeitia
  3. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, 47014, Italy

    • Vincenza Conteduca
  4. Research Department of Oncology, University College London Cancer Institute, London, UK

    • Vincenza Conteduca
    • , Daniel Wetterskog
    • , Anuradha Jayaram
    •  & Gerhardt Attard

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Conflict of interest

GA is on the ICR list of rewards to inventors for abiraterone. GA has received honoraria, consulting fees, or travel support from Astellas, Medivation, Janssen, Millennium Pharmaceuticals, Ipsen, Ventana, ESSA Pharmaceuticals, and Sanofi-Aventis and grant support from Janssen, AstraZeneca, and Arno. EG-B has received speaker honoraria or travel support from Astellas, Janssen-Cilag and Sanofi- Aventis. The other authors declare that they have no conflict of interest.

Corresponding authors

Correspondence to Enrique González-Billalabeitia or Gerhardt Attard.

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https://doi.org/10.1038/s41391-018-0098-x