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Published in: Breast Cancer Research 4/2011

01-08-2011 | Review

Poly(ADP-ribose) polymerase inhibition: a new direction for BRCAand triple-negative breast cancer?

Author: Ruth Plummer

Published in: Breast Cancer Research | Issue 4/2011

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Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARP)-mediated DNA repair have shown promise in early clinical studies in the treatment of specific subgroups of breast cancer. Notably, phase II trials indicate that olaparib, an oral PARP inhibitor, has activity as a single agent in BRCA-related tumours, and that a combination of iniparib, an intravenous PARP inhibitor, and chemotherapy offers a survival advantage, compared with chemotherapy alone, in triple-negative breast cancer. Phase III data on the latter indication are expected in 2011. Intriguingly, iniparib does not increase toxicity when used as a chemo-potentiating agent, suggesting that it differs in its mechanism of action from other agents in this class. Overall, PARP inhibitors represent a potentially important new class of anti-cancer agents with two potential modes of action, as single agents causing synthetic lethality and as chemo-potentiating agents.
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Literature
2.
go back to reference Hery C, Ferlay J, Boniol M, Autier P: Changes in breast cancer incidence and mortality in middle-aged and elderly women in 28 countries with Caucasian majority populations. Ann Oncol. 2008, 19: 1009-1018. 10.1093/annonc/mdm593.CrossRefPubMed Hery C, Ferlay J, Boniol M, Autier P: Changes in breast cancer incidence and mortality in middle-aged and elderly women in 28 countries with Caucasian majority populations. Ann Oncol. 2008, 19: 1009-1018. 10.1093/annonc/mdm593.CrossRefPubMed
3.
go back to reference Tutt A, Robson M, Garber J, Domchek S, Audeh M, Weitzel J, Friedlander M, Carmichael J: Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. J Clin Oncol. 2009, 27 (18s): CRA501- Tutt A, Robson M, Garber J, Domchek S, Audeh M, Weitzel J, Friedlander M, Carmichael J: Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. J Clin Oncol. 2009, 27 (18s): CRA501-
4.
go back to reference Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010, 376: 235-244. 10.1016/S0140-6736(10)60892-6.CrossRefPubMed Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010, 376: 235-244. 10.1016/S0140-6736(10)60892-6.CrossRefPubMed
5.
go back to reference Audeh M, Penson R, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel J, Carmichael J, Tutt A: Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer. J Clin Oncol. 2009, 27 (15s): 5500- Audeh M, Penson R, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel J, Carmichael J, Tutt A: Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer. J Clin Oncol. 2009, 27 (15s): 5500-
6.
go back to reference Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010, 376: 245-251. 10.1016/S0140-6736(10)60893-8.CrossRefPubMed Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010, 376: 245-251. 10.1016/S0140-6736(10)60893-8.CrossRefPubMed
7.
go back to reference Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Giranda VL, Bernhard KM, Habin KR, Ellisen LW, Winer EP, Goss PE: A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer [abstract]. J Clin Oncol. 2010, 28 (Suppl): 1019- Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Giranda VL, Bernhard KM, Habin KR, Ellisen LW, Winer EP, Goss PE: A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer [abstract]. J Clin Oncol. 2010, 28 (Suppl): 1019-
8.
go back to reference Dent RA, Lindeman GJ, Clemons M, Wildiers H, Chan A, McCarthy NJ, Singer CF, Lowe ES, Kemsley K, Carmichael J: Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first-or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial [abstract]. J Clin Oncol. 2010, 28 (Suppl): 1018- Dent RA, Lindeman GJ, Clemons M, Wildiers H, Chan A, McCarthy NJ, Singer CF, Lowe ES, Kemsley K, Carmichael J: Safety and efficacy of the oral PARP inhibitor olaparib (AZD2281) in combination with paclitaxel for the first-or second-line treatment of patients with metastatic triple-negative breast cancer: Results from the safety cohort of a phase I/II multicenter trial [abstract]. J Clin Oncol. 2010, 28 (Suppl): 1018-
9.
go back to reference O'Shaughnessy J, Osborne C, Pippen J, Yoffe M, Patt D, Monaghan G, Rocha C, Ossovskaya V, Sherman B, Sammons B: Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial. J Clin Oncol. 2009, 27 (18s): 3- O'Shaughnessy J, Osborne C, Pippen J, Yoffe M, Patt D, Monaghan G, Rocha C, Ossovskaya V, Sherman B, Sammons B: Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial. J Clin Oncol. 2009, 27 (18s): 3-
10.
go back to reference O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley CR: Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011, 364: 205-214. 10.1056/NEJMoa1011418.CrossRefPubMed O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley CR: Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011, 364: 205-214. 10.1056/NEJMoa1011418.CrossRefPubMed
11.
go back to reference Gelmon KA, Hirte HW, Robidoux A, Tonkin KS, Tischkowitz M, Swenerton K, Huntsman D, Carmichael J, MacPherson E, Oza AM: Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer [abstract]. J Clin Oncol. 2010, 28 (Suppl): 3002- Gelmon KA, Hirte HW, Robidoux A, Tonkin KS, Tischkowitz M, Swenerton K, Huntsman D, Carmichael J, MacPherson E, Oza AM: Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer [abstract]. J Clin Oncol. 2010, 28 (Suppl): 3002-
12.
go back to reference Chambon P, Weil JD, Mandel P: Nicotinamide mononucleotide activation of a new DNA-dependent polyadenylic acid sythesizing nuclear enzyme. Biochem Biophys Res Commun. 1963, 11: 39-43. 10.1016/0006-291X(63)90024-X.CrossRefPubMed Chambon P, Weil JD, Mandel P: Nicotinamide mononucleotide activation of a new DNA-dependent polyadenylic acid sythesizing nuclear enzyme. Biochem Biophys Res Commun. 1963, 11: 39-43. 10.1016/0006-291X(63)90024-X.CrossRefPubMed
13.
go back to reference Ame J, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Murcia J, de Murcia G: PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999, 274: 17860-17868. 10.1074/jbc.274.25.17860.CrossRefPubMed Ame J, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Murcia J, de Murcia G: PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999, 274: 17860-17868. 10.1074/jbc.274.25.17860.CrossRefPubMed
14.
go back to reference Sodhi RK, Singh N, Jaggi AS: Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications. Vascul Pharmacol. 2010, 53: 77-87. 10.1016/j.vph.2010.06.003.CrossRefPubMed Sodhi RK, Singh N, Jaggi AS: Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications. Vascul Pharmacol. 2010, 53: 77-87. 10.1016/j.vph.2010.06.003.CrossRefPubMed
15.
go back to reference Heale JT, Ball AR, Schmiesing JA, Kim J, Kong X, Zhou S, Hudson DF, Earnshaw WC, Yokomori K: Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Mol Cell. 2006, 21: 837-848. 10.1016/j.molcel.2006.01.036.CrossRefPubMed Heale JT, Ball AR, Schmiesing JA, Kim J, Kong X, Zhou S, Hudson DF, Earnshaw WC, Yokomori K: Condensin I interacts with the PARP-1-XRCC1 complex and functions in DNA single-strand break repair. Mol Cell. 2006, 21: 837-848. 10.1016/j.molcel.2006.01.036.CrossRefPubMed
16.
go back to reference Fortini P, Pascucci B, Parlatini E, Errico MD, Dogliotti E: The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie. 2003, 85: 1053-1071. 10.1016/j.biochi.2003.11.003.CrossRefPubMed Fortini P, Pascucci B, Parlatini E, Errico MD, Dogliotti E: The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie. 2003, 85: 1053-1071. 10.1016/j.biochi.2003.11.003.CrossRefPubMed
17.
go back to reference Dantzer F, Schreiber V, Niedergang C, Trucco C, Flatter E, De La Rubia G, Oliver J, Rolli V, Menissier-de Murcia J, de Murcia G: Involvement of poly(ADP-ribose) polymerase in base excision repair. Biochimie. 1999, 81: 69-75. 10.1016/S0300-9084(99)80040-6.CrossRefPubMed Dantzer F, Schreiber V, Niedergang C, Trucco C, Flatter E, De La Rubia G, Oliver J, Rolli V, Menissier-de Murcia J, de Murcia G: Involvement of poly(ADP-ribose) polymerase in base excision repair. Biochimie. 1999, 81: 69-75. 10.1016/S0300-9084(99)80040-6.CrossRefPubMed
19.
go back to reference Bowman KJ, Newell DR, Calvert AH, Curtin NJ: Differential effects of the poly(ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro. Br J Cancer. 2001, 84: 106-112. 10.1054/bjoc.2000.1555.CrossRefPubMedPubMedCentral Bowman KJ, Newell DR, Calvert AH, Curtin NJ: Differential effects of the poly(ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro. Br J Cancer. 2001, 84: 106-112. 10.1054/bjoc.2000.1555.CrossRefPubMedPubMedCentral
20.
go back to reference Canan Koch SS, Thoresen LH, Tikhe JG, Maegley KA, Almassy RJ, Li J, Yu XH, Zook SE, Kumpf RA, Zhang C, Boritzki TJ, Mansour RN, Zhang KE, Ekker A, Calabrese CR, Curtin NJ, Kyle S, Thomas HD, Wang LZ, Calvert AH, Golding BT, Griffin RJ, Newell DR, Webber SE, Hostomsky Z: Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure. J Med Chem. 2002, 45: 4961-4974. 10.1021/jm020259n.CrossRefPubMed Canan Koch SS, Thoresen LH, Tikhe JG, Maegley KA, Almassy RJ, Li J, Yu XH, Zook SE, Kumpf RA, Zhang C, Boritzki TJ, Mansour RN, Zhang KE, Ekker A, Calabrese CR, Curtin NJ, Kyle S, Thomas HD, Wang LZ, Calvert AH, Golding BT, Griffin RJ, Newell DR, Webber SE, Hostomsky Z: Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure. J Med Chem. 2002, 45: 4961-4974. 10.1021/jm020259n.CrossRefPubMed
21.
go back to reference Jones C, Plummer ER: PARP inhibitors and cancer therapy - early results and potential applications. Br J Radiol. 2008, 81: S2-S5. 10.1259/bjr/30872348.CrossRefPubMed Jones C, Plummer ER: PARP inhibitors and cancer therapy - early results and potential applications. Br J Radiol. 2008, 81: S2-S5. 10.1259/bjr/30872348.CrossRefPubMed
22.
go back to reference Plummer R, Jones C, Middleton M, Wilson R, Evans J, Olsen A, Curtin N, Boddy A, McHugh P, Newell D, Harris A, Johnson P, Steinfeldt H, Dewji R, Wang D, Robson L, Calvert H: Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2008, 14: 7917-7923. 10.1158/1078-0432.CCR-08-1223.CrossRefPubMedPubMedCentral Plummer R, Jones C, Middleton M, Wilson R, Evans J, Olsen A, Curtin N, Boddy A, McHugh P, Newell D, Harris A, Johnson P, Steinfeldt H, Dewji R, Wang D, Robson L, Calvert H: Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2008, 14: 7917-7923. 10.1158/1078-0432.CCR-08-1223.CrossRefPubMedPubMedCentral
23.
go back to reference Tentori L, Portarena I, Graziani G: Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors. Pharmacol Res. 2002, 45: 73-85. 10.1006/phrs.2001.0935.CrossRefPubMed Tentori L, Portarena I, Graziani G: Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors. Pharmacol Res. 2002, 45: 73-85. 10.1006/phrs.2001.0935.CrossRefPubMed
24.
go back to reference Graziani G, Szabo C: Clinical perspectives of PARP inhibitors. Pharmacol Res. 2005, 52: 109-118. 10.1016/j.phrs.2005.02.013.CrossRefPubMed Graziani G, Szabo C: Clinical perspectives of PARP inhibitors. Pharmacol Res. 2005, 52: 109-118. 10.1016/j.phrs.2005.02.013.CrossRefPubMed
25.
go back to reference Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005, 434: 913-917. 10.1038/nature03443.CrossRefPubMed Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005, 434: 913-917. 10.1038/nature03443.CrossRefPubMed
26.
go back to reference Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005, 434: 917-921. 10.1038/nature03445.CrossRefPubMed Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005, 434: 917-921. 10.1038/nature03445.CrossRefPubMed
27.
go back to reference Tutt A, Ashworth A: The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol Med. 2002, 8: 571-576. 10.1016/S1471-4914(02)02434-6.CrossRefPubMed Tutt A, Ashworth A: The relationship between the roles of BRCA genes in DNA repair and cancer predisposition. Trends Mol Med. 2002, 8: 571-576. 10.1016/S1471-4914(02)02434-6.CrossRefPubMed
28.
go back to reference Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS: Inhibition of Poly(ADP-Ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009, 361: 123-134. 10.1056/NEJMoa0900212.CrossRefPubMed Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS: Inhibition of Poly(ADP-Ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009, 361: 123-134. 10.1056/NEJMoa0900212.CrossRefPubMed
29.
go back to reference Edwards S, Brough R, Lord C, Natrajan R, Vatcheva R, Levine D, Boyd J, Reis-Filho J, Ashworth A: Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008, 451: 1111-1115. 10.1038/nature06548.CrossRefPubMed Edwards S, Brough R, Lord C, Natrajan R, Vatcheva R, Levine D, Boyd J, Reis-Filho J, Ashworth A: Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008, 451: 1111-1115. 10.1038/nature06548.CrossRefPubMed
30.
go back to reference Sakai W, Swisher EM, Karlan BY, Agarwal MK, Higgins J, Friedman C, Villegas E, Jacquemont C, Farrugia DJ, Couch FJ, Urban N, Taniguchi T: Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008, 451: 1116-1120. 10.1038/nature06633.CrossRefPubMedPubMedCentral Sakai W, Swisher EM, Karlan BY, Agarwal MK, Higgins J, Friedman C, Villegas E, Jacquemont C, Farrugia DJ, Couch FJ, Urban N, Taniguchi T: Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008, 451: 1116-1120. 10.1038/nature06633.CrossRefPubMedPubMedCentral
31.
go back to reference Sandhu SK, Wenham RM, Wilding G, McFadden M, Sun L, Toniatti C, Stroh M, Carpenter CL, de Bono JS, Schelman WR: First-in-human trial of a poly(ADP-ribose) polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (pts) with antitumor activity in BRCA-deficient and sporadic ovarian cancers [abstract]. J Clin Oncol. 2010, 28 (Suppl): 3001- Sandhu SK, Wenham RM, Wilding G, McFadden M, Sun L, Toniatti C, Stroh M, Carpenter CL, de Bono JS, Schelman WR: First-in-human trial of a poly(ADP-ribose) polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (pts) with antitumor activity in BRCA-deficient and sporadic ovarian cancers [abstract]. J Clin Oncol. 2010, 28 (Suppl): 3001-
32.
go back to reference Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, Vredenburgh J, Rich J, Friedman AH, Reardon DA, Sampson JH, Pegg AE, Moschel RC, Birch R, McLendon RE, Provenzale JM, Gururangan S, Dancey JE, Maxwell J, Tourt-Uhlig S, Herndon JE, Bigner DD, Friedman HS: Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005, 23: 7178-7187. 10.1200/JCO.2005.06.502.CrossRefPubMed Quinn JA, Desjardins A, Weingart J, Brem H, Dolan ME, Delaney SM, Vredenburgh J, Rich J, Friedman AH, Reardon DA, Sampson JH, Pegg AE, Moschel RC, Birch R, McLendon RE, Provenzale JM, Gururangan S, Dancey JE, Maxwell J, Tourt-Uhlig S, Herndon JE, Bigner DD, Friedman HS: Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol. 2005, 23: 7178-7187. 10.1200/JCO.2005.06.502.CrossRefPubMed
33.
go back to reference Ranson M, Middleton MR, Bridgewater J, Lee SM, Dawson M, Jowle D, Halbert G, Waller S, McGrath H, Gumbrell L, McElhinney RS, Donnelly D, McMurry TB, Margison GP: Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2006, 12: 1577-1584. 10.1158/1078-0432.CCR-05-2198.CrossRefPubMed Ranson M, Middleton MR, Bridgewater J, Lee SM, Dawson M, Jowle D, Halbert G, Waller S, McGrath H, Gumbrell L, McElhinney RS, Donnelly D, McMurry TB, Margison GP: Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res. 2006, 12: 1577-1584. 10.1158/1078-0432.CCR-05-2198.CrossRefPubMed
34.
go back to reference Schilsky RL, Dolan ME, Bertucci D, Ewesuedo RB, Vogelzang NJ, Mani S, Wilson LR, Ratain MJ: Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancer. Clin Cancer Res. 2000, 6: 3025-3031.PubMed Schilsky RL, Dolan ME, Bertucci D, Ewesuedo RB, Vogelzang NJ, Mani S, Wilson LR, Ratain MJ: Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancer. Clin Cancer Res. 2000, 6: 3025-3031.PubMed
35.
go back to reference Kummar S, Chen AP, Ji JJ, Allen D, Egorin MJ, Gandara DR, Lenz H, Morgan R, Newman EM, Doroshow JH: A phase I study of ABT-888 (A) in combination with metronomic cyclophosphamide (C) in adults with refractory solid tumors and lymphomas [abstract]. J Clin Oncol. 2010, 28 (Suppl): 2605- Kummar S, Chen AP, Ji JJ, Allen D, Egorin MJ, Gandara DR, Lenz H, Morgan R, Newman EM, Doroshow JH: A phase I study of ABT-888 (A) in combination with metronomic cyclophosphamide (C) in adults with refractory solid tumors and lymphomas [abstract]. J Clin Oncol. 2010, 28 (Suppl): 2605-
36.
go back to reference Plummer R, Lorigan P, Evans J, Steven N, Middleton M, Wilson R, Snow K, Dewji R, Calvert H: First and final report of a phase II study of the poly(ADP-ribose) polymerase (PARP) inhibitor, AGO14699, in combination with temozolomide (TMZ) in patients with metastatic malignant melanoma (MM). J Clin Oncol. 2006, 24: 456S-456S. Plummer R, Lorigan P, Evans J, Steven N, Middleton M, Wilson R, Snow K, Dewji R, Calvert H: First and final report of a phase II study of the poly(ADP-ribose) polymerase (PARP) inhibitor, AGO14699, in combination with temozolomide (TMZ) in patients with metastatic malignant melanoma (MM). J Clin Oncol. 2006, 24: 456S-456S.
37.
go back to reference Kummar S, Ji J, Zhang Y, Simmons D, Kinders R, Gutierrez ME, Allen D, Homeffer Y, Juwara L, Rubinstein L, Parchment RE, Murgo AJ, Chen A, Tomaszewski JE, Doroshow JH: A phase I combination study of ABT-888 and topotecan hydrochloride in adults with refractory solid tumors and lymphomas. Ann Oncol. 2009, 20: 42-44. Kummar S, Ji J, Zhang Y, Simmons D, Kinders R, Gutierrez ME, Allen D, Homeffer Y, Juwara L, Rubinstein L, Parchment RE, Murgo AJ, Chen A, Tomaszewski JE, Doroshow JH: A phase I combination study of ABT-888 and topotecan hydrochloride in adults with refractory solid tumors and lymphomas. Ann Oncol. 2009, 20: 42-44.
38.
go back to reference Giaccone G, Rajan A, Kelly RJ, Gutierrez M, Kummar S, Yancey M, Ji JJ, Zhang L, Parchment RE, Doroshow JH: A phase I combination study of olaparib (AZD2281; KU-0059436) and cisplatin (C) plus gemcitabine (G) in adults with solid tumors [abstract]. J Clin Oncol. 2010, 28 (Suppl): 3027- Giaccone G, Rajan A, Kelly RJ, Gutierrez M, Kummar S, Yancey M, Ji JJ, Zhang L, Parchment RE, Doroshow JH: A phase I combination study of olaparib (AZD2281; KU-0059436) and cisplatin (C) plus gemcitabine (G) in adults with solid tumors [abstract]. J Clin Oncol. 2010, 28 (Suppl): 3027-
39.
go back to reference Mahany J, Lewis N, Heath E, LoRusso P, Mita M, Rodon J, Tolcher A, Sherman B, Bradley C, Papadopoulos K: A phase IB study evaluating BSI-201 in combination with chemotherapy in subjects with advanced solid tumors. J Clin Oncol. 2008, 26 (Suppl): 3579- Mahany J, Lewis N, Heath E, LoRusso P, Mita M, Rodon J, Tolcher A, Sherman B, Bradley C, Papadopoulos K: A phase IB study evaluating BSI-201 in combination with chemotherapy in subjects with advanced solid tumors. J Clin Oncol. 2008, 26 (Suppl): 3579-
40.
go back to reference Bartsch R, Ziebermayr R, Zielinski CC, Steger GG: Triple-negative breast cancer. Wien Med Wochenschr. 2010, 160: 174-181. 10.1007/s10354-010-0773-6.CrossRefPubMed Bartsch R, Ziebermayr R, Zielinski CC, Steger GG: Triple-negative breast cancer. Wien Med Wochenschr. 2010, 160: 174-181. 10.1007/s10354-010-0773-6.CrossRefPubMed
41.
go back to reference Kopetz S, Mita M, Mok I, Sankhala K, Moseley J, Sherman B, Bradley C, Tolcher A: First in human phase I study of BSI-201, a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in subjects with advanced solid tumors. J Clin Oncol. 2008, 26 (Suppl): 3577- Kopetz S, Mita M, Mok I, Sankhala K, Moseley J, Sherman B, Bradley C, Tolcher A: First in human phase I study of BSI-201, a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in subjects with advanced solid tumors. J Clin Oncol. 2008, 26 (Suppl): 3577-
42.
go back to reference Blakeley JO, Ye X, Grossman SA, Mikkelsen T, Rosenfeld MR, Bradley CR, Eichler AF, Nabors LB, Desideri S, Supko JG: Poly (ADP-ribose) polymerase-1 (PARP1) inhibitor BSI-201 in combination with temozolomide (TMZ) in malignant glioma [abstract]. J Clin Oncol. 2010, 28 (Suppl): 2012- Blakeley JO, Ye X, Grossman SA, Mikkelsen T, Rosenfeld MR, Bradley CR, Eichler AF, Nabors LB, Desideri S, Supko JG: Poly (ADP-ribose) polymerase-1 (PARP1) inhibitor BSI-201 in combination with temozolomide (TMZ) in malignant glioma [abstract]. J Clin Oncol. 2010, 28 (Suppl): 2012-
Metadata
Title
Poly(ADP-ribose) polymerase inhibition: a new direction for BRCAand triple-negative breast cancer?
Author
Ruth Plummer
Publication date
01-08-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2877

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