Journal article
Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition
J Goodall, J Mateo, W Yuan, H Mossop, N Porta, S Miranda, R Perez-Lopez, D Dolling, DR Robinson, S Sandhu, G Fowler, B Ebbs, P Flohr, G Seed, DN Rodrigues, G Boysen, C Bertan, M Atkin, M Clarke, M Crespo Show all
Cancer Discovery | AMER ASSOC CANCER RESEARCH | Published : 2017
Abstract
Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity associating with homologous recombination DNA repair defects. We now report targeted and whole-exome sequencing of serial circulating cellfree DNA (cfDNA) samples collected during this trial. Decreases in cfDNA concentration independently associated with outcome in multivariable analyses (HR for overall survival at week 8: 0.19; 95% CI, 0.06-0.56; P = 0.003). All tumor tissue somatic DNA repair mutations were detectable in cfDNA; allele frequency of somatic mutations decre..
View full abstractGrants
Awarded by Prostate Cancer Foundation
Funding Acknowledgements
We would like to acknowledge funding support from Movember (Movember/PCUKCEO13-2-002); Prostate Cancer Foundation (PCF grant 20131017); Prostate Cancer UK (PCUK PG12-49); a Stand Up To Cancer-Prostate Cancer Foundation Prostate Dream Team Translational Cancer Research Grant (SU2C-AACR-DT0712; PCF grants 20131017 and 20131017-1); Cancer Research UK (Centre Programme grant); Experimental Cancer Medicine Centre grant funding from Cancer Research UK and the Department of Health; and Biomedical Research Centre funding to the Royal Marsden (ECMC CRM064X). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. TOPARP is an investigator-initiated study supported by Cancer Research UK (grants C12540/A12829, C12540/A13230, C1491/A9895, and C1491/A15955) and conducted with support from the Investigator-Sponsored Study Collaboration between AstraZeneca and the National Institute for Health Research Cancer Research Network. J. Mateo was supported by a Prostate Cancer Foundation (PCF) Young Investigator Award (PCF-16-YOUN11) and a Prostate Cancer UK-Medical Research Council Fellowship (MR/M003272/1). S. Sandhu was supported by the Prostate Cancer Foundation of Australia. G. Seed was supported by a Prostate Cancer UK PhD Studentship (TLD-S15-006). A. Sharp was supported by a Medical Research Council Fellowship (MR/M018618/1).