Skip to main content
Erschienen in: Targeted Oncology 5/2016

11.07.2016 | Review Article

Investigating BRCA Mutations: A Breakthrough in Precision Medicine of Castration-Resistant Prostate Cancer

verfasst von: Alessandra Modena, Roberto Iacovelli, Aldo Scarpa, Matteo Brunelli, Chiara Ciccarese, Emanuela Fantinel, Davide Bimbatti, Francesco Massari, Guido Martignoni, Giampaolo Tortora

Erschienen in: Targeted Oncology | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

Despite the development of novel effective therapeutic strategies, metastatic castration-resistant prostate cancer (mCRPC) remains a disease with a lethal course and a high biological and molecular heterogeneity. To date, germline mutations in the BRCA gene represent one of the main risk factors for developing prostate cancer, with a strong association with aggressive phenotype and poor clinical outcomes. A better understanding of the genomic landscape of prostate cancer has strengthened the idea that “synthetic lethality” of this disease might be useful in cancer-drug discovery, focusing on agents such as platinum compounds and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). In this review, we summarize the main data available on BRCA mutations and discuss the clinical implications of these genomic aberrations in the management of prostate cancer, stressing the need to identify prognostic and predictive biomarkers and to deeply understand the mechanisms of treatment resistance, in order to maximize personalized medicine protocols and therefore clinical benefit.
https://static-content.springer.com/image/art%3A10.1007%2Fs11523-016-0450-9/MediaObjects/11523_2016_450_Figa_HTML.gif
Literatur
1.
Zurück zum Zitat Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. doi:10.1002/ijc.29210.CrossRefPubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. doi:10.​1002/​ijc.​29210.CrossRefPubMed
4.
Zurück zum Zitat Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12. doi:10.1056/NEJMoa040720.CrossRefPubMed Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12. doi:10.​1056/​NEJMoa040720.CrossRefPubMed
5.
Zurück zum Zitat Petrylak DP, Tangen CM, Hussain MH, Lara Jr PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20. doi:10.1056/NEJMoa041318.CrossRefPubMed Petrylak DP, Tangen CM, Hussain MH, Lara Jr PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20. doi:10.​1056/​NEJMoa041318.CrossRefPubMed
6.
Zurück zum Zitat Bracarda S, Sisani M, Marrocolo F, Hamzaj A, Del Buono S, Altavilla A. Clinical implications for a treatment algorithm and differential indication to hormone therapy and chemotherapy options in metastatic castrate-resistant prostate cancer: a personal view. Expert Rev Anticancer Ther. 2014;14(11):1283–94. doi:10.1586/14737140.2014.965686.CrossRefPubMed Bracarda S, Sisani M, Marrocolo F, Hamzaj A, Del Buono S, Altavilla A. Clinical implications for a treatment algorithm and differential indication to hormone therapy and chemotherapy options in metastatic castrate-resistant prostate cancer: a personal view. Expert Rev Anticancer Ther. 2014;14(11):1283–94. doi:10.​1586/​14737140.​2014.​965686.CrossRefPubMed
7.
Zurück zum Zitat de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–54. doi:10.1016/S0140-6736(10)61389-X.CrossRefPubMed de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–54. doi:10.​1016/​S0140-6736(10)61389-X.CrossRefPubMed
8.
Zurück zum Zitat Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983–92. doi:10.1016/S1470-2045(12)70379-0.CrossRefPubMed Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983–92. doi:10.​1016/​S1470-2045(12)70379-0.CrossRefPubMed
9.
Zurück zum Zitat Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152–60. doi:10.1016/S1470-2045(14)71205-7.CrossRefPubMed Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152–60. doi:10.​1016/​S1470-2045(14)71205-7.CrossRefPubMed
10.
Zurück zum Zitat Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97. doi:10.1056/NEJMoa1207506.CrossRefPubMed Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97. doi:10.​1056/​NEJMoa1207506.CrossRefPubMed
12.
Zurück zum Zitat Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Rathkopf DE, Loriot Y, et al. Enzalutamide (ENZA) in men with chemotherapy-Naive metastatic castration-resistant prostate cancer (mCRPC): Final analysis of the phase 3 PREVAIL study. J Clin Oncol 33, 2015 (suppl; abstr 5036). Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Rathkopf DE, Loriot Y, et al. Enzalutamide (ENZA) in men with chemotherapy-Naive metastatic castration-resistant prostate cancer (mCRPC): Final analysis of the phase 3 PREVAIL study. J Clin Oncol 33, 2015 (suppl; abstr 5036).
13.
14.
15.
Zurück zum Zitat van Soest RJ, van Royen ME, de Morree ES, Moll JM, Teubel W, Wiemer EA, et al. Cross-resistance between taxanes and new hormonal agents abiraterone and enzalutamide may affect drug sequence choices in metastatic castration-resistant prostate cancer. Eur J Cancer. 2013;49(18):3821–30. doi:10.1016/j.ejca.2013.09.026.CrossRefPubMed van Soest RJ, van Royen ME, de Morree ES, Moll JM, Teubel W, Wiemer EA, et al. Cross-resistance between taxanes and new hormonal agents abiraterone and enzalutamide may affect drug sequence choices in metastatic castration-resistant prostate cancer. Eur J Cancer. 2013;49(18):3821–30. doi:10.​1016/​j.​ejca.​2013.​09.​026.CrossRefPubMed
16.
Zurück zum Zitat Bahl A, Masson S, Birtle A, Chowdhury S, de Bono J. Second-line treatment options in metastatic castration-resistant prostate cancer: a comparison of key trials with recently approved agents. Cancer Treat Rev. 2014;40(1):170–7. doi:10.1016/j.ctrv.2013.06.008.CrossRefPubMed Bahl A, Masson S, Birtle A, Chowdhury S, de Bono J. Second-line treatment options in metastatic castration-resistant prostate cancer: a comparison of key trials with recently approved agents. Cancer Treat Rev. 2014;40(1):170–7. doi:10.​1016/​j.​ctrv.​2013.​06.​008.CrossRefPubMed
18.
Zurück zum Zitat Attard G, Swennenhuis JF, Olmos D, Reid AH, Vickers E, A’Hern 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(7):2912–8. doi:10.1158/0008-5472.CAN-08-3667.CrossRefPubMed Attard G, Swennenhuis JF, Olmos D, Reid AH, Vickers E, A’Hern 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(7):2912–8. doi:10.​1158/​0008-5472.​CAN-08-3667.CrossRefPubMed
20.
Zurück zum Zitat Mehra R, Han B, Tomlins SA, Wang L, Menon A, Wasco MJ, et al. Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res. 2007;67(17):7991–5. doi:10.1158/0008-5472.CAN-07-2043.CrossRefPubMed Mehra R, Han B, Tomlins SA, Wang L, Menon A, Wasco MJ, et al. Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate adenocarcinoma: molecular evidence for an independent group of diseases. Cancer Res. 2007;67(17):7991–5. doi:10.​1158/​0008-5472.​CAN-07-2043.CrossRefPubMed
24.
Zurück zum Zitat Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N, et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer. 2011;105(8):1230–4. doi:10.1038/bjc.2011.383.CrossRefPubMedPubMedCentral Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N, et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer. 2011;105(8):1230–4. doi:10.​1038/​bjc.​2011.​383.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Myers CE, Feldman R, Abbott BL, Reddy SK, Castro M. Frequency of BRCA mutations and co-occurring alterations in prostate cancer. J Clin Oncol 34, 2016 (suppl 2S; abstr 289). Myers CE, Feldman R, Abbott BL, Reddy SK, Castro M. Frequency of BRCA mutations and co-occurring alterations in prostate cancer. J Clin Oncol 34, 2016 (suppl 2S; abstr 289).
26.
Zurück zum Zitat Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(3):244–50. doi:10.1200/JCO.2014.56.2728.CrossRef Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(3):244–50. doi:10.​1200/​JCO.​2014.​56.​2728.CrossRef
29.
Zurück zum Zitat Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002;108(2):171–82.CrossRefPubMed Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002;108(2):171–82.CrossRefPubMed
31.
Zurück zum Zitat Yoshida K, Miki Y. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 2004;95(11):866–71.CrossRefPubMed Yoshida K, Miki Y. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 2004;95(11):866–71.CrossRefPubMed
32.
Zurück zum Zitat Martin AM, Blackwood MA, Antin-Ozerkis D, Shih HA, Calzone K, Colligon TA, et al. Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic. J Clin Oncol. 2001;19(8):2247–53.PubMed Martin AM, Blackwood MA, Antin-Ozerkis D, Shih HA, Calzone K, Colligon TA, et al. Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic. J Clin Oncol. 2001;19(8):2247–53.PubMed
34.
Zurück zum Zitat Gudmundsson J, Johannesdottir G, Bergthorsson JT, Arason A, Ingvarsson S, Egilsson V, et al. Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13. Cancer Res. 1995;55(21):4830–2.PubMed Gudmundsson J, Johannesdottir G, Bergthorsson JT, Arason A, Ingvarsson S, Egilsson V, et al. Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13. Cancer Res. 1995;55(21):4830–2.PubMed
35.
Zurück zum Zitat Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121(2):269–75. doi:10.1002/cncr.29041.CrossRefPubMed Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121(2):269–75. doi:10.​1002/​cncr.​29041.CrossRefPubMed
36.
Zurück zum Zitat Edwards SM, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, et al. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet. 2003;72(1):1–12.CrossRefPubMed Edwards SM, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, et al. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet. 2003;72(1):1–12.CrossRefPubMed
38.
Zurück zum Zitat Giusti RM, Rutter JL, Duray PH, Freedman LS, Konichezky M, Fisher-Fischbein J, et al. A twofold increase in BRCA mutation related prostate cancer among Ashkenazi Israelis is not associated with distinctive histopathology. J Med Genet. 2003;40(10):787–92.CrossRefPubMedPubMedCentral Giusti RM, Rutter JL, Duray PH, Freedman LS, Konichezky M, Fisher-Fischbein J, et al. A twofold increase in BRCA mutation related prostate cancer among Ashkenazi Israelis is not associated with distinctive histopathology. J Med Genet. 2003;40(10):787–92.CrossRefPubMedPubMedCentral
40.
42.
Zurück zum Zitat Tryggvadottir L, Vidarsdottir L, Thorgeirsson T, Jonasson JG, Olafsdottir EJ, Olafsdottir GH, et al. Prostate cancer progression and survival in BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99(12):929–35. doi:10.1093/jnci/djm005.CrossRefPubMed Tryggvadottir L, Vidarsdottir L, Thorgeirsson T, Jonasson JG, Olafsdottir EJ, Olafsdottir GH, et al. Prostate cancer progression and survival in BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99(12):929–35. doi:10.​1093/​jnci/​djm005.CrossRefPubMed
46.
Zurück zum Zitat Thorne H, Willems AJ, Niedermayr E, Hoh IM, Li J, Clouston D, et al. Decreased prostate cancer-specific survival of men with BRCA2 mutations from multiple breast cancer families. Cancer Prev Res. 2011;4(7):1002–10. doi:10.1158/1940-6207.CAPR-10-0397.CrossRef Thorne H, Willems AJ, Niedermayr E, Hoh IM, Li J, Clouston D, et al. Decreased prostate cancer-specific survival of men with BRCA2 mutations from multiple breast cancer families. Cancer Prev Res. 2011;4(7):1002–10. doi:10.​1158/​1940-6207.​CAPR-10-0397.CrossRef
47.
48.
Zurück zum Zitat Castro E, Goh C, Leongamornlert D, Saunders E, Tymrakiewicz M, Dadaev T, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol. 2015;68(2):186–93. doi:10.1016/j.eururo.2014.10.022.CrossRefPubMed Castro E, Goh C, Leongamornlert D, Saunders E, Tymrakiewicz M, Dadaev T, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol. 2015;68(2):186–93. doi:10.​1016/​j.​eururo.​2014.​10.​022.CrossRefPubMed
49.
Zurück zum Zitat Kim SH, Park WS, Yun SI, Joo J, Joung JY, Seo HK, et al. Overexpression of BRCA1 or BRCA2 in prostatectomy specimens is predictive of biochemical recurrence after radical prostatectomy. Histopathology. 2015. doi:10.1111/his.12809. Kim SH, Park WS, Yun SI, Joo J, Joung JY, Seo HK, et al. Overexpression of BRCA1 or BRCA2 in prostatectomy specimens is predictive of biochemical recurrence after radical prostatectomy. Histopathology. 2015. doi:10.​1111/​his.​12809.
50.
Zurück zum Zitat Hartwell LH, Szankasi P, Roberts CJ, Murray AW, Friend SH. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997;278(5340):1064–8.CrossRefPubMed Hartwell LH, Szankasi P, Roberts CJ, Murray AW, Friend SH. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997;278(5340):1064–8.CrossRefPubMed
51.
Zurück zum Zitat Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28(3):375–9. doi:10.1200/JCO.2008.20.7019.CrossRefPubMed Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28(3):375–9. doi:10.​1200/​JCO.​2008.​20.​7019.CrossRefPubMed
53.
Zurück zum Zitat Tan DS, Rothermundt C, Thomas K, Bancroft E, Eeles R, Shanley S, et al. “BRCAness” syndrome in ovarian cancer: a case–control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J Clin Oncol. 2008;26(34):5530–6. doi:10.1200/JCO.2008.16.1703.CrossRefPubMed Tan DS, Rothermundt C, Thomas K, Bancroft E, Eeles R, Shanley S, et al. “BRCAness” syndrome in ovarian cancer: a case–control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J Clin Oncol. 2008;26(34):5530–6. doi:10.​1200/​JCO.​2008.​16.​1703.CrossRefPubMed
55.
Zurück zum Zitat Sella A, Yarom N, Zisman A, Kovel S. Paclitaxel, estramustine and carboplatin combination chemotherapy after initial docetaxel-based chemotherapy in castration-resistant prostate cancer. Oncology. 2009;76(6):442–6. doi:10.1159/000217264.CrossRefPubMed Sella A, Yarom N, Zisman A, Kovel S. Paclitaxel, estramustine and carboplatin combination chemotherapy after initial docetaxel-based chemotherapy in castration-resistant prostate cancer. Oncology. 2009;76(6):442–6. doi:10.​1159/​000217264.CrossRefPubMed
57.
Zurück zum Zitat Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol. 2009;27(32):5431–8. doi:10.1200/JCO.2008.20.1228.CrossRefPubMed Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol. 2009;27(32):5431–8. doi:10.​1200/​JCO.​2008.​20.​1228.CrossRefPubMed
59.
Zurück zum Zitat Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol. 2010;28(15):2512–9. doi:10.1200/JCO.2009.26.9589.CrossRefPubMed Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol. 2010;28(15):2512–9. doi:10.​1200/​JCO.​2009.​26.​9589.CrossRefPubMed
60.
62.
Zurück zum Zitat Dantzer F, de La Rubia G, Menissier-De Murcia J, Hostomsky Z, de Murcia G, Schreiber V. Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1. Biochemistry. 2000;39(25):7559–69.CrossRefPubMed Dantzer F, de La Rubia G, Menissier-De Murcia J, Hostomsky Z, de Murcia G, Schreiber V. Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1. Biochemistry. 2000;39(25):7559–69.CrossRefPubMed
63.
Zurück zum Zitat Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–7. doi:10.1038/nature03443.CrossRefPubMed Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–7. doi:10.​1038/​nature03443.CrossRefPubMed
64.
65.
Zurück zum Zitat Tutt AN, Lord CJ, McCabe N, Farmer H, Turner N, Martin NM, et al. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb Symp Quant Biol. 2005;70:139–48. doi:10.1101/sqb.2005.70.012.CrossRefPubMed Tutt AN, Lord CJ, McCabe N, Farmer H, Turner N, Martin NM, et al. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb Symp Quant Biol. 2005;70:139–48. doi:10.​1101/​sqb.​2005.​70.​012.CrossRefPubMed
67.
Zurück zum Zitat Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21. doi:10.1038/nature03445.CrossRefPubMed Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21. doi:10.​1038/​nature03445.CrossRefPubMed
68.
69.
70.
Zurück zum Zitat Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013;14(9):882–92. doi:10.1016/S1470-2045(13)70240-7.CrossRefPubMed Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013;14(9):882–92. doi:10.​1016/​S1470-2045(13)70240-7.CrossRefPubMed
71.
Zurück zum Zitat Hussain M, Carducci MA, Slovin S, Cetnar J, Qian J, McKeegan EM, et al. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer. Investig New Drugs. 2014;32(5):904–12. doi:10.1007/s10637-014-0099-0.CrossRef Hussain M, Carducci MA, Slovin S, Cetnar J, Qian J, McKeegan EM, et al. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer. Investig New Drugs. 2014;32(5):904–12. doi:10.​1007/​s10637-014-0099-0.CrossRef
74.
Zurück zum Zitat Hussain M, Daignault S, Twardowski P, Albany C, Stein MN, Kunju LP, et al. Co-targeting androgen receptor (AR) and DNA repair: a randomized ETS gene fusion-stratified trial of abiraterone + prednisone (Abi) +/− the PARP1 inhibitor veliparib for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) (NCI9012)--a University of Chicago phase II consortium trial. J Clin Oncol 34, 2016 (suppl; abstr 5010). Hussain M, Daignault S, Twardowski P, Albany C, Stein MN, Kunju LP, et al. Co-targeting androgen receptor (AR) and DNA repair: a randomized ETS gene fusion-stratified trial of abiraterone + prednisone (Abi) +/− the PARP1 inhibitor veliparib for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) (NCI9012)--a University of Chicago phase II consortium trial. J Clin Oncol 34, 2016 (suppl; abstr 5010).
76.
78.
Metadaten
Titel
Investigating BRCA Mutations: A Breakthrough in Precision Medicine of Castration-Resistant Prostate Cancer
verfasst von
Alessandra Modena
Roberto Iacovelli
Aldo Scarpa
Matteo Brunelli
Chiara Ciccarese
Emanuela Fantinel
Davide Bimbatti
Francesco Massari
Guido Martignoni
Giampaolo Tortora
Publikationsdatum
11.07.2016
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 5/2016
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-016-0450-9

Weitere Artikel der Ausgabe 5/2016

Targeted Oncology 5/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.