Review Article | Published:

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

Prostate Cancer and Prostatic Diseases (2018) | Download Citation


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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

  2. 2.

    Gillessen S, Attard G, Beer TM, Beltran H, Bossi A, Bristow R. et al. Management of patients with advanced prostate cancer: the report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol. 2018;73:178–211.

  3. 3.

    Attard G, Parker C, Eeles RA, Schröder F, Tomlins SA, Tannock I, et al. Prostate cancer. Lancet. 2016;387:70–82.

  4. 4.

    Grasso CS, Wu Y-M, Robinson DR, Cao X, Dhanasekaran SM, Khan AP. et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487:239–43.

  5. 5.

    Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate. Cancer Cell. 2015;161:1215–28.

  6. 6.

    Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481:306–13.

  7. 7.

    Schmitt MW, Loeb LA, Salk JJ. The influence of subclonal resistance mutations on targeted cancer therapy. Nat Rev Clin Oncol. 2016;13:335–47.

  8. 8.

    Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S. et al. Tracking the evolution of non–small-cell lung cancer. N Engl J Med. 2017;376:2109–21.

  9. 9.

    Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520:353–7.

  10. 10.

    Kumar A, Coleman I, Morrissey C, Zhang X, True LD, Gulati R, et al. Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. Nat Med. 2016;22:369–78.

  11. 11.

    Beltran H, Prandi D, Mosquera JM, Benelli M, Puca L, Cyrta J, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med. 2016;22:298–305.

  12. 12.

    Taplin ME. Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663. J Clin Oncol. 2003;21:2673–8.

  13. 13.

    Henzler C, Li Y, Yang R, McBride T, Ho Y, Sprenger C, et al. Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer. Nat Commun. 2016;7:1–12.

  14. 14.

    Perez-Gracia JL, Sanmamed MF, Bosch A, Patiño-Garcia A, Schalper KA, Segura V, et al. Strategies to design clinical studies to identify predictive biomarkers in cancer research. Cancer Treat Rev. 2017;53:79–97.

  15. 15.

    Schwarzenbach H, Hoon DSB, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11:426–37.

  16. 16.

    Lorente D, Mateo J, de Bono JS. Molecular characterization and clinical utility of circulating tumor cells in the treatment of prostate cancer. Am Soc Clin Oncol Educ Book. 2014;34:e197–203.

  17. 17.

    Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4:650–61.

  18. 18.

    Nawaz M, Camussi G, Valadi H, Nazarenko I, Ekström K, Wang X, et al. The emerging role of extracellular vesicles as biomarkers for urogenital cancers. Nat Rev Urol. 2014;11:688–701.

  19. 19.

    Mandel P, Métais P. Les acides nucleiques du plasma sanguin chez l’homme. C R Seances Soc Biol Fil. 1948;142:241–3.

  20. 20.

    Beiter T, Fragasso A, Hudemann J, Niess AM, Simon P. Short-term treadmill running as a model for studying cell-free DNA kinetics in vivo. Clin Chem. 2011;57:633–6.

  21. 21.

    Antonatos D, Patsilinakos S, Spanodimos S, Korkonikitas P, Tsigas D. Cell-free DNA levels as a prognostic marker in acute myocardial infarction. Ann NY Acad Sci. 2006;1075:278–81.

  22. 22.

    Swaminathan R, Butt AN. Circulating nucleic acids in plasma and serum: recent developments. Ann NY Acad Sci. 2006;1075:1–9.

  23. 23.

    Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350:485–7.

  24. 24.

    Lo YM. Fetal DNA in maternal plasma: biology and diagnostic applications. Clin Chem. 2000;46:1903–6.

  25. 25.

    Bianchi DW. From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges. Nat Med. 2012;18:1041–51.

  26. 26.

    Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature. 2017;61:69.

  27. 27.

    Diaz LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32:579–86.

  28. 28.

    Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2007;14:985–90.

  29. 29.

    Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61:1659–65.

  30. 30.

    Jiang P, Chan CWM, Chan KCA, Cheng SH, Wong J, Wong VW-S, et al. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients. Proc Natl Acad Sci USA. 2015;112:E1317–25.

  31. 31.

    Lo YMD, Chan KCA, Sun H, Chen EZ, Jiang P, Lun FMF. et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med. 2010;2:61ra91

  32. 32.

    Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell. 2016;164:57–68.

  33. 33.

    Ivanov M, Baranova A, Butler T, Spellman P, Mileyko V. Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation. BMC Genom. 2015;16(Suppl 13):S1.

  34. 34.

    Schwarzenbach H, Müller V, Milde-Langosch K, Steinbach B, Pantel K. Evaluation of cell-free tumour DNA and RNA in patients with breast cancer and benign breast disease. Mol Biosyst. 2011;7:2848–54.

  35. 35.

    Sozzi G, Conte D, Leon M, Cirincione R, Roz L, Ratcliffe C, et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. J Clin Oncol. 2003;21:3902–8.

  36. 36.

    Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, Fernandez-Perez MP, Jayaram A. et al. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann Oncol. 2017;28:1508–16.

  37. 37.

    De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, nez-Ricarte FMI, Torrejon D, et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015;6:1–6.

  38. 38.

    Lu T, Li J. Clinical applications of urinary cell-free DNA in cancer: current insights and promising future. Am J Cancer Res. 2017;7:2318–32.

  39. 39.

    Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer--a survey. Biochim Biophys Acta. 2007;1775:181–232.

  40. 40.

    Dawson S-J, Tsui DWY, Murtaza M, Biggs H, Rueda OM, Chin S-F, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368:1199–209.

  41. 41.

    Romanel A, Tandefelt DG, Conteduca V, Jayaram A, Casiraghi N, Wetterskog D, et al. Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med. 2015;7:312re10.

  42. 42.

    Murtaza M, Dawson S-J, Tsui DWY, Gale D, Forshew T, Piskorz AM, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497:108–12.

  43. 43.

    Vogelstein B, Kinzler KW. Digital PCR. Proc Natl Acad Sci USA. 1999;96:9236–41.

  44. 44.

    Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C, Duncan C. et al. Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med. 2010;2:20ra14

  45. 45.

    Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D. et al. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci Transl Med. 2012;4:162ra154

  46. 46.

    Carreira S, Romanel A, Goodall J, Grist E, Ferraldeschi R, Miranda S. et al. Tumor clone dynamics in lethal prostate cancer. Sci Transl Med. 2014;6:254ra125

  47. 47.

    De Laere B, van Dam P-J, Whitington T, Mayrhofer M, Diaz EH, Van den Eynden G. et al. Comprehensive profiling of the androgen receptor in liquid biopsies from castration-resistant prostate cancer reveals novel intra-AR structural variation and splice variant expression patterns. Eur Urol. 2017;72:192–200.

  48. 48.

    Newman AM, Lovejoy AF, Klass DM, Kurtz DM, Chabon JJ, Scherer F, et al. Integrated digital error suppression for improved detection of circulating tumor DNA. Nat Biotechnol. 2016;34:547–55.

  49. 49.

    Seed G, Yuan W, Mateo J, Carreira S, Bertan C, Lambros M, et al. Gene copy number estimation from targeted next-generation sequencing of prostate cancer biopsies: analytic validation and clinical qualification. Clin Cancer Res. 2017;23:6070–7.

  50. 50.

    Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S. et al. Circulating free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov. 2017;7:1006–17.

  51. 51.

    Quigley D, Alumkal JJ, Wyatt AW, Kothari V, Foye A, Lloyd P. et al. Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors. Cancer Discov. 2017;7:999–1005.

  52. 52.

    Grasso CS, Wu Y-M, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487:239–43.

  53. 53.

    Abida W, Armenia J, Gopalan A, Brennan R, Walsh M, Barron D, et al. Prospective genomic profiling of prostate cancer across disease states reveals germline and somatic alterations that may affect clinical decision making. JCO Precis Oncol. 2017;2017:1–16.

  54. 54.

    TCGAR Network, Abeshouse A, Ahn J, Akbani R, Ally A, Amin S, et al. The molecular taxonomy of primary prostate. Cancer Cell. 2015;163:1011–25.

  55. 55.

    Fraser M, Sabelnykova VY, Yamaguchi TN, Heisler LE, Livingstone J, Huang V, et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature. 2017;541:359–64.

  56. 56.

    Richter E, Srivastava S, Dobi A. Androgen receptor and prostate cancer. Prostate Cancer Prostatic Dis. 2007;10:114–8.

  57. 57.

    Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66:2815–25.

  58. 58.

    Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25:276–308.

  59. 59.

    Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787–90.

  60. 60.

    Annala M, Vandekerkhove G, Khalaf D, Taavitsainen S, Beja K, Warner EW, et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov. 2018;8:444–57.

  61. 61.

    Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995;332:1393–8.

  62. 62.

    Tan J, Sharief Y, Hamil KG, Gregory CW, Zang DY, Sar M, et al. Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol. 1997;11:450–9.

  63. 63.

    Azad AA, Volik SV, Wyatt AW, Haegert A, Le Bihan S, Bell RH, et al. Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin Cancer Res. 2015;21:2315–24.

  64. 64.

    Chen EJ, Sowalsky AG, Gao S, Cai C, Voznesensky O, Schaefer R, et al. Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors. Clin Cancer Res. 2015;21:1273–80.

  65. 65.

    Balbas MD, Evans MJ, Hosfield DJ, Wongvipat J, Arora VK, Watson PA. et al. Overcoming mutation-based resistance to antiandrogens with rational drug design. ELife. 2013;2:e00499

  66. 66.

    Joseph JD, Lu N, Qian J, Sensintaffar J, Shao G, Brigham D, et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov. 2013;3:1020–9.

  67. 67.

    Wyatt AW, Azad AA, Volik SV, Annala M, Beja K, McConeghy B. et al. Genomic alterations in cell-free DNA and enzalutamide resistance in castration-resistant prostate cancer. JAMA Oncol . 2016;2:1598–1606.

  68. 68.

    Salvi S, Casadio V, Conteduca V, Lolli C, Gurioli G, Martignano F, et al. Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. Oncotarget. 2016;7:37839–45.

  69. 69.

    Salvi S, Casadio V, Conteduca V, Burgio SL, Menna C, Bianchi E, et al. Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone. Br J Cancer. 2015;112:1717–24.

  70. 70.

    Molina A, Rathkopf DE, Fizazi K, Kantoff PW, Li J, Azad AA, et al. A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. Ann Oncol. 2016;27:454–60.

  71. 71.

    Halabi S, Lin CY, Kelly WK, Fizazi KS, Moul JW, Kaplan EB, et al. Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2014;32:671–7.

  72. 72.

    Scher HI, Heller G, Molina A, Attard G, Danila DC, Jia X, et al. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015;33:1348–55.

  73. 73.

    Conteduca V, Jayaram A, Romero-Laorden N, Wetterskog D, Salvi S, Gurioli G, et al. Plasma androgen receptor (pAR) status and activity of taxanes in metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2018;36 (suppl; abstr 5074).

  74. 74.

    Jayaram A, Wetterskog D, Attard G. Plasma DNA and metastatic castration-resistant prostate cancer: the odyssey to a clinical biomarker test. Cancer Discov. 2018;8:392–4.

  75. 75.

    Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol. 2013;31:1748–57.

  76. 76.

    Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.

  77. 77.

    Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373:1697–708.

  78. 78.

    Cheng HH, Pritchard CC, Boyd T, Nelson PS, Montgomery B. Biallelic inactivation of BRCA2 in platinum-sensitive metastatic castration-resistant prostate cancer. Eur Urol. 2016;69:992–5.

  79. 79.

    Annala M, Struss WJ, Warner EW, Beja K, Vandekerkhove G, Wong A, et al. Treatment outcomes and tumor loss of heterozygosity in germline DNA repair–deficient prostate cancer. Eur Urol. 2017;72:34–42.

  80. 80.

    Wyatt AW, Annala M, Aggarwal R, Beja K, Feng F, Youngren J, et al. Concordance of circulating tumor DNA and matched metastatic tissue biopsy in prostate cancer. J Natl Cancer Inst. 2017;110:1–9.

  81. 81.

    Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S, et al. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov. 2017;7:1006–17.

  82. 82.

    Norquist B, Wurz KA, Pennil CC, Garcia R, Gross J, Sakai W, et al. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J Clin Oncol. 2011;29:3008–15.

  83. 83.

    Afghahi A, Timms KM, Vinayak S, Jensen KC, Kurian AW, Carlson RW, et al. Tumor BRCA1 reversion mutation arising during neoadjuvant platinum-based chemotherapy in triple-negative breast cancer is associated with therapy resistance. Clin Cancer Res. 2017;23:3365–70.

  84. 84.

    Castro E, Laorden NR, Rodriguez JMP, del Pozo A, Sáez MI, Colmenero AM. et al. LBA32 PROREPAIR-B: a prospective cohort study of DNA repair defects in metastatic castration resistant prostate cancer (mCRPC). Ann Oncol. 2017;28:mdx440.025

  85. 85.

    Mateo J, Cheng HH, Beltran H, Dolling D, Xu W, Pritchard CC. et al. Clinical outcome of prostate cancer patients with germline DNA repair mutations: retrospective analysis from an International Study. Eur Urol . 2018;73:687–93.

  86. 86.

    Hussain M, Daignault-Newton S, Twardowski PW, Albany C, Stein MN, Kunju LP, et al. Targeting androgen receptor and DNA repair in metastatic castration-resistant prostate cancer: results from NCI 9012. J Clin Oncol. 2018;36:991–9.

  87. 87.

    Antonarakis ES, Lu C, Luber B, Liang C, Wang H, Chen Y. et al. Germline DNA-repair gene mutations and outcomes in men with metastatic castration-resistant prostate cancer receiving first-line abiraterone and enzalutamide. Eur Urol. 2018;74:218–25.

  88. 88.

    Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen C-C, et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 2017;355:84–88.

  89. 89.

    Ku S-Y, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science. 2017;355:78–83.

  90. 90.

    Lunardi A, Ala U, Epping MT, Salmena L, Clohessy JG, Webster KA. et al. A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer. Nat Genet. 2013;45:747–55.

  91. 91.

    Ulz P, Belic J, Graf R, Auer M, Lafer I, Fischereder K, et al. Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer. Nat Commun. 2016;7:12008–12.

  92. 92.

    Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19:575–86.

  93. 93.

    de Bono JS, De Giorgi U, Massard C, Bracarda S, Rodrigues DN, Kocak I. et al. PTEN loss as a predictive biomarker for the Akt inhibitor ipatasertib combined with abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2016;27:7180

  94. 94.

    Annala M, Vandekerkhove G, Khalaf D, Taavitsainen S, Beja K, Warner EW. et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov. 2018;8:444–57.

  95. 95.

    Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.

  96. 96.

    Gonzalez Billalabeitia E, Seitzer N, Song SJ, Song MS, Patnaik A, Liu X-S, et al. Vulnerabilities of PTEN-TP53-deficient prostate cancers to compound PARP-PI3K inhibition. Cancer Discov. 2014;4:896–904.

  97. 97.

    Patnaik A, Swanson KD, Csizmadia E, Solanki A, Landon-Brace N, Gehring MP, et al. Cabozantinib eradicates advanced murine prostate cancer by activating antitumor innate immunity. Cancer Discov. 2017;7:750–65.

  98. 98.

    Chun FKH, Muller I, Lange I, Friedrich MG, Erbersdobler A, Karakiewicz PI, et al. Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer. BJU Int. 2006;98:544–8.

  99. 99.

    Antonarakis ES, Lu C, Luber B, Wang H, Chen Y, Zhu Y, et al. Clinical significance of androgen receptor splice variant-7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line abiraterone and enzalutamide. J Clin Oncol. 2017;35:2149–56.

  100. 100.

    Scher HI, Lu D, Schreiber NA, Louw J, Graf RP, Vargas HA, et al. Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol. 2016;2:1441–10.

Download references

Author information

Author notes

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


  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


  1. Search for Enrique González-Billalabeitia in:

  2. Search for Vincenza Conteduca in:

  3. Search for Daniel Wetterskog in:

  4. Search for Anuradha Jayaram in:

  5. Search for Gerhardt Attard in:

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.

About this article

Publication history