Molecular Biomarkers in Prostate Cancer: Comparison
Please note this is a comparison between Version 2 by Bruce Ren and Version 1 by Fernando López Campos.

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the differential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients.

  • biomarkers
  • DNA repair
  • gene panels
  • genetic testing
  • germline mutation
  • precision medicine
  • prostate cancer
  • prostate genomics
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References

  1. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30.
  2. Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015, 65, 87–108.
  3. Larrañaga, N.; Galceran, J.; Ardanaz, E.; Franch, P.; Navarro, C.; Sánchez, M.J.; Pastor-Barriuso, R.; Martos, C.; Rodríguez, L.; Vilardell, L.; et al. Prostate cancer incidence trends in Spain before and during the prostate-specific antigen era: Impact on mortality. Ann. Oncol. 2010, 21, iii83–iii89.
  4. Hugosson, J.; Carlsson, S.; Aus, G.; Bergdahl, S.; Khatami, A.; Lodding, P.; Pihl, C.G.; Stranne, J.; Holmberg, E.; Lilja, H. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010, 11, 725–732.
  5. Graif, T.; Loeb, S.; Roehl, K.A.; Gashti, S.N.; Griffin, C.; Yu, X.; Catalona, W.J. Under Diagnosis and Over Diagnosis of Prostate Cancer. J. Urol. 2007, 178, 88–92.
  6. Schröder, F.H.; Hugosson, J.; Roobol, M.J.; Tammela, T.L.J.; Ciatto, S.; Nelen, V.; Kwiatkowski, M.; Lujan, M.; Lilja, H.; Zappa, M.; et al. Screening and prostate-cancer mortality in a randomized european study. N. Engl. J. Med. 2009, 360, 1320–1328.
  7. Nelson, W.G.; Carter, H.B.; DeWeese, T.L.; Antonarakis, E.S.; Eisenberger, M.A. Prostate Cancer. Abeloff’s Clin. Oncol. Fifth Ed. 2014, 1463–1496.e9.
  8. Amin, M.B.; Edge, S.; Greene, F.; Byrd, D.R.; Brookland, R.K.; Washington, M.K.; Gershenwald, J.E. AJCC Cancer Staging Form Supplement, 8th ed.; American Joint Committee on Cancer: Chicago, IL, USA, 2018.
  9. D’Amico, A.V.; Whittington, R.; Kaplan, I.; Beard, C.; Jiroutek, M.; Malkowicz, S.B.; Wein, A.; Coleman, C.N. Equivalent biochemical failure-free survival after external beam radiation therapy or radical prostatectomy in patients with a pretreatment prostate specific antigen of > 4-20 ng/mL. Int. J. Radiat. Oncol. Biol. Phys. 1997, 37, 1053–1058.
  10. Angeles, A.; Bauer, S.; Ratz, L.; Klauck, S.; Sültmann, H. Genome-Based Classification and Therapy of Prostate Cancer. Diagnostics 2018, 8, 62.
  11. Shipitsin, M.; Small, C.; Choudhury, S.; Giladi, E.; Friedlander, S.; Nardone, J.; Hussain, S.; Hurley, A.D.; Ernst, C.; Huang, Y.E.; et al. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error. Br. J. Cancer 2014, 111, 1201–1212.
  12. Blume-Jensen, P.; Berman, D.M.; Rimm, D.L.; Shipitsin, M.; Putzi, M.; Nifong, T.P.; Small, C.; Choudhury, S.; Capela, T.; Coupal, L.; et al. Biology of Human Tumors Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clin. Cancer Res. 2015, 21, 2591–2600.
  13. Cuzick, J.; Swanson, G.P.; Fisher, G.; Brothman, A.R.; Berney, D.M.; Reid, J.E.; Mesher, D.; Speights, V.O.; Stankiewicz, E.; Foster, C.S.; et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: A retrospective study. Lancet Oncol. 2011, 12, 245–255.
  14. Cuzick, J.; Berney, D.M.; Fisher, G.; Mesher, D.; Møller, H.; Reid, J.E.; Perry, M.; Park, J.; Younus, A.; Gutin, A.; et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br. J. Cancer 2012, 106, 1095–1099.
  15. Eggener, S.E.; Rumble, R.B.; Armstrong, A.J.; Morgan, T.M.; Crispino, T.; Cornford, P.; van der Kwast, T.; Grignon, D.J.; Rai, A.J.; Agarwal, N.; et al. Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline. J. Clin. Oncol. 2020, 13, 1474–1494.
  16. Cooperberg, M.R.; Simko, J.P.; Cowan, J.E.; Reid, J.E.; Djalilvand, A.; Bhatnagar, S.; Gutin, A.; Lanchbury, J.S.; Swanson, G.P.; Stone, S.; et al. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J. Clin. Oncol. 2013, 31, 1428–1434.
  17. Freedland, S.J.; Gerber, L.; Reid, J.; Welbourn, W.; Tikishvili, E.; Park, J.; Younus, A.; Gutin, A.; Sangale, Z.; Lanchbury, J.S.; et al. Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 2013, 86, 848–853.
  18. Advice, N. NICE Advice - Prolaris gene expression assay for assessing long-term risk of prostate cancer progression: © NICE (2016) Prolaris gene expression assay for assessing long-term risk of prostate cancer progression. BJU Int. 2018, 122, 173–180.
  19. López, I.H.; Parada, D.; Gallardo, P.; Gascón, M.; Besora, A.; Peña, K.; Riu, F.; Arquez Pianetta, M.; Abuchaibe, O.; Torres Royò, L.; et al. Prognostic correlation of cell cycle progression score and Ki-67 as a predictor of aggressiveness, biochemical failure, and mortality in men with high-risk prostate cancer treated with external beam radiation therapy. Reports Pract. Oncol. Radiother. 2017, 22, 251–257.
  20. Klein, E.A.; Cooperberg, M.R.; Magi-Galluzzi, C.; Simko, J.P.; Falzarano, S.M.; Maddala, T.; Chan, J.M.; Li, J.; Cowan, J.E.; Tsiatis, A.C.; et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur. Urol. 2014, 66, 550–560.
  21. Cullen, J.; Rosner, I.L.; Brand, T.C.; Zhang, N.; Tsiatis, A.C.; Moncur, J.; Ali, A.; Chen, Y.; Knezevic, D.; Maddala, T.; et al. A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur. Urol. 2015, 68, 123–131.
  22. Lin, D.W.; Zheng, Y.; McKenney, J.K.; Brown, M.D.; Lu, R.; Crager, M.; Boyer, H.; Tretiakova, M.; Brooks, J.D.; Dash, A.; et al. 17-Gene Genomic Prostate Score Test Results in the Canary Prostate Active Surveillance Study (PASS) Cohort. J. Clin. Oncol. 2020, 38, 1549–1557.
  23. Marascio, J.; Spratt, D.E.; Zhang, J.; Trabulsi, E.J.; Le, T.; Sedzorme, W.S.; Beeler, W.H.; Davicioni, E.; Dabbas, B.; Lin, D.W.; et al. Prospective study to define the clinical utility and benefit of Decipher testing in men following prostatectomy. Prostate Cancer Prostatic Dis. 2019.
  24. Spratt, D.E.; Yousefi, K.; Deheshi, S.; Ross, A.E.; Den, R.B.; Schaeffer, E.M.; Trock, B.J.; Zhang, J.; Glass, A.G.; Dicker, A.P.; et al. Individual patient-level meta-Analysis of the performance of the decipher genomic classifier in high-risk men after prostatectomy to predict development of metastatic disease. J. Clin. Oncol. 2017, 35, 1991–1998.
  25. Dalela, D.; Santiago-Jiménez, M.; Yousefi, K.; Karnes, R.J.; Ross, A.E.; Den, R.B.; Freedland, S.J.; Schaeffer, E.M.; Dicker, A.P.; Menon, M.; et al. Genomic classifier augments the role of pathological features in identifying optimal candidates for adjuvant radiation therapy in patients with prostate cancer: Development and internal validation of a multivariable prognostic model. J. Clin. Oncol. 2017, 35, 1982–1990.
  26. Gore, J.L.; du Plessis, M.; Santiago-Jiménez, M.; Yousefi, K.; Thompson, D.J.S.; Karsh, L.; Lane, B.R.; Franks, M.; Chen, D.Y.T.; Bandyk, M.; et al. Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study. Cancer 2017, 123, 2850–2859.
  27. Den, R.B.; Feng, F.Y.; Showalter, T.N.; Mishra, M.V.; Trabulsi, E.J.; Lallas, C.D.; Gomella, L.G.; Kelly, W.K.; Birbe, R.C.; McCue, P.A.; et al. Genomic prostate cancer classifier predicts biochemical failure and metastases in patients after postoperative radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 2014, 89, 1038–1046.
  28. Zhao, S.G.; Chang, S.L.; Spratt, D.E.; Erho, N.; Yu, M.; Ashab, H.A.D.; Alshalalfa, M.; Speers, C.; Tomlins, S.A.; Davicioni, E.; et al. Development and validation of a 24-gene predictor of response to postoperative radiotherapy in prostate cancer: A matched, retrospective analysis. Lancet Oncol. 2016, 17, 1612–1620.
  29. Kim, H.L.; Li, P.; Huang, H.C.; Deheshi, S.; Marti, T.; Knudsen, B.; Abou-Ouf, H.; Alam, R.; Lotan, T.L.; Lam, L.L.C.; et al. Validation of the Decipher Test for predicting adverse pathology in candidates for prostate cancer active surveillance. Prostate Cancer Prostatic Dis. 2019, 22, 399–405.
  30. Berlin, A.; Murgic, J.; Hosni, A.; Pintilie, M.; Salcedo, A.; Fraser, M.; Kamel-Reid, S.; Zhang, J.; Wang, Q.; Ch’ng, C.; et al. Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy. Int. J. Radiat. Oncol. Biol. Phys. 2019, 103, 84–91.
  31. Feng, F.Y.; Sandler, H.M.; Huang, H.-C.; Simko, J.; Davicioni, E.; Nguyen, P.L.; Efstathiou, J.A.; Dicker, A.P.; Dignam, J.J.; Seiferheld, W.; et al. Transcriptome profiling of NRG Oncology/RTOG 9601: Validation of a prognostic genomic classifier in salvage radiotherapy prostate cancer patients from a prospective randomized trial. J. Clin. Oncol. 2020, 38, 276.
  32. Cuzick, J.; Stone, S.; Fisher, G.; Yang, Z.H.; North, B.V.; Berney, D.M.; Beltran, L.; Greenberg, D.; Møller, H.; Reid, J.E.; et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br. J. Cancer 2015, 113, 382–389.
  33. Castro, E.; Goh, C.; Leongamornlert, D.; Saunders, E.; Tymrakiewicz, M.; Dadaev, T.; Govindasami, K.; Guy, M.; Ellis, S.; Frost, D.; et al. Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival after Radical Treatment for Localised Prostate Cancer. Eur. Urol. 2015, 68, 186–193.
  34. Giri, V.N.; Knudsen, K.E.; Kelly, W.K.; Abida, W.; Andriole, G.L.; Bangma, C.H.; Bekelman, J.E.; Benson, M.C.; Blanco, A.; Burnett, A.; et al. Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017. J. Clin. Oncol. 2018, 36, 414–424.
  35. Thorne, H.; Willems, A.J.; Niedermayr, E.; Hoh, I.M.Y.; Li, J.; Clouston, D.; Mitchell, G.; Fox, S.; Hopper, J.L.; Bolton, D. Decreased prostate cancer-specific survival of men with BRCA2 mutations from multiple breast cancer families. Cancer Prev. Res. 2011, 4, 1002–1010.
  36. Castro, E.; Eeles, R. The role of BRCA1 and BRCA2 in prostate cancer. Asian J. Androl. 2012, 14, 409–414.
  37. Das, S.; Salami, S.S.; Spratt, D.E.; Kaffenberger, S.D.; Jacobs, M.F.; Morgan, T.M. Bringing Prostate Cancer Germline Genetics into Clinical Practice. J. Urol. 2019, 202, 223–230.
  38. Gallagher, D.J.; Gaudet, M.M.; Pal, P.; Kirchhoff, T.; Balistreri, L.; Vora, K.; Bhatia, J.; Stadler, Z.; Fine, S.W.; Reuter, V.; et al. Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin. Cancer Res. 2010, 16, 2115–2121.
  39. Armenia, J.; Wankowicz, S.A.M.; Liu, D.; Gao, J.; Kundra, R.; Reznik, E.; Chatila, W.K.; Chakravarty, D.; Han, G.C.; Coleman, I.; et al. The long tail of oncogenic drivers in prostate cancer. Nat. Genet. 2018, 50, 645–651.
  40. Grasso, C.S.; Wu, Y.M.; Robinson, D.R.; Cao, X.; Dhanasekaran, S.M.; Khan, A.P.; Quist, M.J.; Jing, X.; Lonigro, R.J.; Brenner, J.C.; et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 2012, 487, 239–243.
  41. Robinson, D.; Van Allen, E.M.; Wu, Y.M.; Schultz, N.; Lonigro, R.J.; Mosquera, J.M.; Montgomery, B.; Taplin, M.E.; Pritchard, C.C.; Attard, G.; et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015, 161, 1215–1228.
  42. Pritchard, C.C.; Mateo, J.; Walsh, M.F.; De Sarkar, N.; Abida, W.; Beltran, H.; Garofalo, A.; Gulati, R.; Carreira, S.; Eeles, R.; et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N. Engl. J. Med. 2016, 375, 443–453.
  43. Castro, E.; Romero-Laorden, N.; Del Pozo, A.; Lozano, R.; Medina, A.; Puente, J.; Piulats, J.M.; Lorente, D.; Saez, M.I.; Morales-Barrera, R.; et al. Prorepair-B: A prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J. Clin. Oncol. 2019, 37, 490–503.
  44. Abida, W.; Armenia, J.; Gopalan, A.; Brennan, R.; Walsh, M.; Barron, D.; Danila, D.; Rathkopf, D.; Morris, M.; Slovin, S.; 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, 1–16.
  45. Abida, W.; Cyrta, J.; Heller, G.; Prandi, D.; Armenia, J.; Coleman, I.; Cieslik, M.; Benelli, M.; Robinson, D.; Van Allen, E.M.; et al. Genomic correlates of clinical outcome in advanced prostate cancer. Proc. Natl. Acad. Sci. USA 2019, 166, 11428–11436.
  46. Abeshouse, A.; Ahn, J.; Akbani, R.; Ally, A.; Amin, S.; Andry, C.D.; Annala, M.; Aprikian, A.; Armenia, J.; Arora, A.; et al. The Molecular Taxonomy of Primary Prostate Cancer. Cell 2015, 163, 1011–1025.
  47. Hussain, M.; Mateo, J.; Fizazi, K.; Saad, F.; Shore, N.D.; Sandhu, S.; Chi, K.N.; Sartor, O.; Agarwal, N.; Olmos, D.; et al. PROfound: Phase III study of olaparib versus enzalutamide or abiraterone for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene alterations. Ann. Oncol. 2019, 30, v881–v882.
  48. Mateo, J.; Seed, G.; Bertan, C.; Rescigno, P.; Dolling, D.; Figueiredo, I.; Miranda, S.; Nava Rodrigues, D.; Gurel, B.; Clarke, M.; et al. Genomics of lethal prostate cancer at diagnosis and castration resistance. J. Clin. Investig. 2020, 130, 1743–1751.
  49. Mateo, J.; Porta, N.; Bianchini, D.; McGovern, U.; Elliott, T.; Jones, R.; Syndikus, I.; Ralph, C.; Jain, S.; Varughese, M.; et al. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): A multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020, 21, 162–174.
  50. Mateo, J.; Carreira, S.; Sandhu, S.; Miranda, S.; Mossop, H.; Perez-Lopez, R.; Nava Rodrigues, D.; Robinson, D.; Omlin, A.; Tunariu, N.; et al. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 2015, 373, 1697–1708.
  51. Abida, W.; Campbell, D.; Patnaik, A.; Sautois, B.; Shapiro, J.; Vogelzang, N.J.; Bryce, A.H.; McDermott, R.; Ricci, F.; Rowe, J.; et al. Preliminary results from the TRITON2 study of rucaparib in patients (pts) with DNA damage repair (DDR)-deficient metastatic castration-resistant prostate cancer (mCRPC): Updated analyses. Ann. Oncol. 2019, 30, v327–v328.
  52. Abida, W.; Campbell, D.; Patnaik, A.; Shapiro, J.D.; Sautois, B.; Vogelzang, N.J.; Voog, E.G.; Bryce, A.H.; McDermott, R.; Ricci, F.; et al. Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis from the phase 2 TRITON2 study. Clin. Cancer Res. 2020, 26, 2487–2496.
  53. Smith, M.R.; Sandhu, S.K.; Kelly, W.K.; Scher, H.I.; Efstathiou, E.; Lara, P.N.; Yu, E.Y.; George, D.J.; Chi, K.N.; Saad, F.; et al. Pre-specified interim analysis of GALAHAD: A phase II study of niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD). Ann. Oncol. 2019, 30, v884–v885.
  54. Cheng, H.H.; Pritchard, C.C.; Boyd, T.; Nelson, P.S.; Montgomery, B. Biallelic Inactivation of BRCA2 in Platinum-sensitive Metastatic Castration-resistant Prostate Cancer. Eur. Urol. 2016, 69, 992–995.
  55. Pomerantz, M.M.; Spisák, S.; Jia, L.; Cronin, A.M.; Csabai, I.; Ledet, E.; Sartor, A.O.; Rainville, I.; O’Connor, E.P.; Herbert, Z.T.; et al. The association between germline BRCA2 variants and sensitivity to platinum-based chemotherapy among men with metastatic prostate cancer. Cancer 2017, 123, 3532–3539.
  56. Zafeiriou, Z.; Bianchini, D.; Chandler, R.; Rescigno, P.; Yuan, W.; Carreira, S.; Barrero, M.; Petremolo, A.; Miranda, S.; Riisnaes, R.; et al. Genomic Analysis of Three Metastatic Prostate Cancer Patients with Exceptional Responses to Carboplatin Indicating Different Types of DNA Repair Deficiency. Eur. Urol. 2019, 75, 184–192.
  57. Jonsson, P.; Bandlamudi, C.; Cheng, M.L.; Srinivasan, P.; Chavan, S.S.; Friedman, N.D.; Rosen, E.Y.; Richards, A.L.; Bouvier, N.; Selcuklu, S.D.; et al. Tumour lineage shapes BRCA-mediated phenotypes. Nature 2019, 571, 576–579.
  58. Goodall, J.; Mateo, J.; Yuan, W.; Mossop, H.; Porta, N.; Miranda, S.; Perez-Lopez, R.; Dolling, D.; Robinson, D.R.; Sandhu, S.; et al. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov. 2017, 7, 1006–1017.
  59. Annala, M.; Struss, W.J.; Warner, E.W.; Beja, K.; Vandekerkhove, G.; Wong, A.; Khalaf, D.; Seppälä, I.L.; So, A.; Lo, G.; et al. Treatment Outcomes and Tumor Loss of Heterozygosity in Germline DNA Repair–deficient Prostate Cancer. Eur. Urol. 2017, 72, 34–42.
  60. Mateo, J.; Cheng, H.H.; Beltran, H.; Dolling, D.; Xu, W.; Pritchard, C.C.; Mossop, H.; Rescigno, P.; Perez-Lopez, R.; Sailer, V.; et al. Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study. Eur. Urol. 2018, 73, 687–693.
  61. Antonarakis, E.S.; Lu, C.; Luber, B.; Liang, C.; Wang, H.; Chen, Y.; Silberstein, J.L.; Piana, D.; Lai, Z.; 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, 218–225.
  62. Pritchard, C.C.; Morrissey, C.; Kumar, A.; Zhang, X.; Smith, C.; Coleman, I.; Salipante, S.J.; Milbank, J.; Yu, M.; Grady, W.M.; et al. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat. Commun. 2014, 5, 1–6.
  63. Beltran, H. DNA mismatch repair in prostate cancer. J. Clin. Oncol. 2013, 31, 1782–1784.
  64. Abida, W.; Cheng, M.L.; Armenia, J.; Middha, S.; Autio, K.A.; Vargas, H.A.; Rathkopf, D.; Morris, M.J.; Danila, D.C.; Slovin, S.F.; et al. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2019, 5, 471–478.
  65. Gillentine, M.A.; Berry, L.N.; Goin-Kochel, R.P.; Ali, M.A.; Ge, J.; Guffey, D.; Rosenfeld, J.A.; Hannig, V.; Bader, P.; Proud, M.; et al. The cognitive and behavioral phenotypes of individuals with CHRNA7 duplications. J. Autism Dev. Disord. 2017, 47, 549–562.
  66. Antonarakis, E.S.; Piulats, J.M.; Gross-Goupil, M.; Goh, J.; Ojamaa, K.; Hoimes, C.J.; Vaishampayan, U.; Berger, R.; Sezer, A.; Alanko, T.; et al. Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: Multicohort, open-label phase II KEYNOTE-199 study. J. Clin. Oncol. 2020, 38, 395–405.
  67. Jamaspishvili, T.; Berman, D.M.; Ross, A.E.; Scher, H.I.; De Marzo, A.M.; Squire, J.A.; Lotan, T.L. Clinical implications of PTEN loss in prostate cancer. Nat. Rev. Urol. 2018, 15, 222–234.
  68. Carreira, S.; Romanel, A.; Goodall, J.; Grist, E.; Ferraldeschi, R.; Miranda, S.; Prandi, D.; Lorente, D.; Frenel, J.S.; Pezaro, C.; et al. Tumor clone dynamics in lethal prostate cancer. Sci. Transl. Med. 2014, 6, 254ra125.
  69. Attard, G.; Swennenhuis, J.F.; Olmos, D.; Reid, A.H.M.; Vickers, E.; A’Hern, R.; Levink, R.; Coumans, F.; Moreira, J.; Riisnaes, R.; et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 2009, 69, 2912–2918.
  70. Correia, N.C.; Gírio, A.; Antunes, I.; Martins, L.R.; Barata, J.T. The multiple layers of non-genetic regulation of PTEN tumour suppressor activity. Eur. J. Cancer 2014, 50, 216–225.
  71. Lotan, T.L.; Gurel, B.; Sutcliffe, S.; Esopi, D.; Liu, W.; Xu, J.; Hicks, J.L.; Park, B.H.; Humphreys, E.; Partin, A.W.; et al. PTEN protein loss by immunostaining: Analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin. Cancer Res. 2011, 17, 6563–6573.
  72. Ahearn, T.U.; Pettersson, A.; Ebot, E.M.; Gerke, T.; Graff, R.E.; Morais, C.L.; Hicks, J.L.; Wilson, K.M.; Rider, J.R.; Sesso, H.D.; et al. A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer. J. Natl. Cancer Inst. 2016, 108, 1–9.
  73. Carver, B.S.; Chapinski, C.; Wongvipat, J.; Hieronymus, H.; Chen, Y.; Chandarlapaty, S.; Arora, V.K.; Le, C.; Koutcher, J.; Scher, H.; et al. Reciprocal Feedback Regulation of PI3K and Androgen Receptor Signaling in PTEN-Deficient Prostate Cancer. Cancer Cell 2011, 19, 575–586.
  74. De Bono, J.S.; De Giorgi, U.; Rodrigues, D.N.; Massard, C.; Bracarda, S.; Font, A.; Arija, J.A.A.; Shih, K.C.; Radavoi, G.D.; Xu, N.; et al. Randomized phase II study evaluating AKT blockade with ipatasertib, in combination with abiraterone, in patients with metastatic prostate cancer with and without PTEN loss. Clin. Cancer Res. 2019, 25, 928–936.
  75. Annala, M.; Vandekerkhove, G.; Khalaf, D.; Taavitsainen, S.; Beja, K.; Warner, E.W.; Sunderland, K.; Kollmannsberger, C.; Eigl, B.J.; Finch, D.; et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov. 2018, 8, 444–457.
  76. Conteduca, V.; Wetterskog, D.; Sharabiani, M.T.A.; Grande, E.; Fernandez-Perez, M.P.; Jayaram, A.; Salvi, S.; Castellano, D.; Romanel, A.; Lolli, C.; 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, 1–9.
  77. Conteduca, V.; Castro, E.; Wetterskog, D.; Scarpi, E.; Jayaram, A.; Romero-Laorden, N.; Olmos, D.; Gurioli, G.; Lolli, C.; Sáez, M.I.; et al. Plasma AR status and cabazitaxel in heavily treated metastatic castration-resistant prostate cancer. Eur. J. Cancer 2019, 116, 158–168.
  78. Romanel, A.; Tandefelt, D.G.; Conteduca, V.; Jayaram, A.; Casiraghi, N.; Wetterskog, D.; Salvi, S.; Amadori, D.; Zafeiriou, Z.; Rescigno, P.; et al. Plasma AR and abiraterone-resistant prostate cancer. Sci. Transl. Med. 2015, 7, 1–9.
  79. Antonarakis, E.S.; Lu, C.; Wang, H.; Luber, B.; Nakazawa, M.; Roeser, J.C.; Chen, Y.; Mohammad, T.A.; Chen, Y.; Fedor, H.L.; et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med. 2014, 371, 1028–1038.
  80. Antonarakis, E.S.; Lu, C.; Luber, B.; Wang, H.; Chen, Y.; Nakazawa, M.; Nadal, R.; Paller, C.J.; Denmeade, S.R.; Carducci, M.A.; et al. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol. 2015, 1, 582–591.
  81. Antonarakis, E.S.; Lu, C.; Luber, B.; Wang, H.; Chen, Y.; Zhu, Y.; Silberstein, J.L.; Taylor, M.N.; Maughan, B.L.; Denmeade, S.R.; 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 & second-line Abiraterone & Enzalutamide. J. Clin. Oncol. 2017, 35, 2149–2156.
  82. Scher, H.I.; Graf, R.P.; Schreiber, N.A.; McLaughlin, B.; Lu, D.; Louw, J.; Danila, D.C.; Dugan, L.; Johnson, A.; Heller, G.; et al. Nuclear-specific AR-V7 Protein Localization is Necessary to Guide Treatment Selection in Metastatic Castration-resistant Prostate Cancer. Eur. Urol. 2017, 71, 874–882.
  83. Armstrong, A.J.; Halabi, S.; Luo, J.; Nanus, D.M.; Giannakakou, P.; Szmulewitz, R.Z.; Danila, D.C.; Healy, P.; Anand, M.; Rothwell, C.J.; et al. Prospective multicenter validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer: The PROPHECY study. J. Clin. Oncol. 2019, 37, 120–1129.
  84. De Laere, B.; Oeyen, S.; Mayrhofer, M.; Whitington, T.; van Dam, P.J.; Van Oyen, P.; Ghysel, C.; Ampe, J.; Ost, P.; Demey, W.; et al. TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer. Clin. Cancer Res. 2019, 25, 1766–1773.
  85. Hamid, A.A.; Gray, K.P.; Shaw, G.; MacConaill, L.E.; Evan, C.; Bernard, B.; Loda, M.; Corcoran, N.M.; Van Allen, E.M.; Choudhury, A.D.; et al. Compound Genomic Alterations of TP53, PTEN, and RB1 Tumor Suppressors in Localized and Metastatic Prostate Cancer. Eur. Urol. 2019, 76, 89–97.
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