Efficacy of PARP inhibitor rucaparib in orthotopic glioblastoma xenografts is limited by ineffective drug penetration into the central nervous system

Molecular Cancer Therapeutics

Volumn 14, Issue 12, 2015, Pages 2735-2743

  Parrish, Karen E ^a   Cen, Ling ^b   Murray, James ^c   Calligaris, David ^d   Kizilbash, Sani ^b   Mittapalli, Rajendar K ^a   Carlson, Brett L ^b   Schroeder, Mark A ^b   Sludden, Julieann ^c   Boddy, Alan V ^c   Agar, Nathalie Y R ^d   Curtin, Nicola J ^c   Elmquist, William F ^a   Sarkaria, Jann N ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b MAYO CLINIC   (United States)

^c NEWCASTLE UNIVERSITY   (United Kingdom)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PLACEBO; RUCAPARIB; TEMOZOLOMIDE; VELIPARIB; VINBLASTINE; ZOSUQUIDAR; ABC TRANSPORTER; ABCB1 PROTEIN, HUMAN; ABCG2 PROTEIN, MOUSE; BREAST CANCER RESISTANCE PROTEIN; DACARBAZINE; INDOLE DERIVATIVE; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 3; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN-TO-PLASMA RATIO; CANCER COMBINATION CHEMOTHERAPY; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG PENETRATION; DRUG POTENTIATION; GLIOBLASTOMA; HUMAN; HUMAN CELL; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; DOG; DRUG EFFECTS; DRUG SCREENING; GENETICS; KNOCKOUT MOUSE; MDCK CELL LINE; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; ATP BINDING CASSETTE TRANSPORTER, SUB-FAMILY G, MEMBER 2; ATP-BINDING CASSETTE TRANSPORTERS; CELL LINE, TUMOR; CENTRAL NERVOUS SYSTEM; DACARBAZINE; DOGS; GLIOBLASTOMA; HUMANS; INDOLES; MADIN DARBY CANINE KIDNEY CELLS; MICE; MICE, KNOCKOUT; P-GLYCOPROTEINS; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84952369377     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-15-0553     Document Type: Article

References (50)

1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-96.
2. Hegi ME, Diserens A-C, Gorlia T,HamouM-F, de Tribolet N, Weller M, et al. MGMT Gene silencing and benefit from temozolomide in glioblastoma.N Engl J Med 2005;352:997-1003.
3. Bowman KJ, White A, Golding BT, Griffin RJ, Curtin NJ. Potentiation of anti-cancer agent cytotoxicity by the potent poly(ADP-ribose) polymerase inhibitors NU1025 and NU1064. Br J Cancer 1998;78: 1269-77.
4. Tentori L, Leonetti C, Scarsella M, d'Amati G, Portarena I, Zupi G, et al. Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival ofmice bearing hematologic malignancy at the central nervous system site. Blood 2002;99:2241-4.
5. Miknyoczki SJ, Jones-Bolin S, Pritchard S, Hunter K, Zhao H,Wan W, et al. Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly(ADP-ribose) polymerase inhibitor. Mol Cancer Ther 2003;2:371-82.
6. Calabrese CR, Almassy R, Barton S, Batey MA, Calvert AH, Canan-Koch S, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst 2004;96:56-67.
7. Donawho CK, Luo Y, Penning TD, Bauch JL, Bouska JJ, Bontcheva-Diaz VD, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 2007;13:2728-37.
8. Curtin NJ, Szabo C. Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. Mol Aspects Med 2013;34:1217-56.
9. Daniel RA, Rozanska AL, Mulligan EA, Drew Y, Thomas HD, Castelbuono DJ, et al. Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699. Br J Cancer 2010; 103:1588-96.
10. Thomas HD, Calabrese CR, Batey MA, Canan S, Hostomsky Z, Kyle S, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther 2007;6:945-56.
11. Daniel RA, Rozanska AL, Thomas HD, Mulligan EA, Drew Y, Castelbuono DJ, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res 2009;15:1241-9.
12. Plummer R, Jones C,MiddletonM,Wilson R, Evans J,Olsen A, et al. 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;14:7917-23.
13. Plummer R, Lorigan P, Steven N, Scott L, Middleton MR, Wilson RH, et al. A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation. Cancer Chemother Pharmacol 2013;71:1191-9.
14. Bernhard EJ, McKenna WG, Muschel RJ. Cyclin expression and G2-phase delay after irradiation. Radiat Res 1994;138:S64-S7.
15. Ascierto PA, Simeone E, Giannarelli D, GrimaldiAM, Romano A,Mozzillo N. Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med 2012;10:107.
16. Chu EY, Wanat KA, Miller CJ, Amaravadi RK, Fecher LA, Brose MS, et al. Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. J Am Acad Dermatol 2012;67:1265-72.
17. Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, et al. Dabrafenib in patientswithmelanoma, untreated brainmetastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 2012;379:1893-901.
18. Gibney GT, Sondak VK. Extending the reach of BRAF-targeted cancer therapy. Lancet 2012;379:1858-9.
19. Simeone E, De Maio E, Sandomenico F, Fulciniti F, Lastoria S, Aprea P, et al. Neoplastic leptomeningitis presenting in a melanoma patient treated with dabrafenib (a V600EBRAF inhibitor): a case report. J Med Case Rep 2012; 6:131.
20. KitangeGJ,Mladek AC, Carlson BL, SchroederMA, Pokorny JL, Cen L, et al. Inhibition of histone deacetylation potentiates the evolution of acquired temozolomide resistance linked to MGMT upregulation in glioblastoma xenografts. Clin Cancer Res 2012;18:4070-9.
21. Agarwal S, Sane R, Gallardo JL, Ohlfest JR, Elmquist WF. Distribution of gefitinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux. J Pharmacol Exp Ther 2010;334:147-55.
22. Carlson BL, Pokorny JL, Schroeder MA, Sarkaria JN. Establishment, maintenance, and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery. Curr Protoc Pharmacol 2011;52:14.6.1-.6.23.
23. Agarwal S, Mittapalli RK, Zellmer DM, Gallardo JL, Donelson R, Seiler C, et al. Active efflux of Dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents. Mol Cancer Ther 2012;11:2183-92.
24. Mittapalli RK, Vaidhyanathan S, Sane R, Elmquist WF. Impact of Pglycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) on the brain distribution of a novel BRAF inhibitor: vemurafenib (PLX4032). J Pharmacol Exp Ther 2012;342:33-40.
25. Liu X, Ide JL, Norton I, Marchionni MA, Ebling MC, Wang LY, et al. Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging. Sci Rep 2013;3:2859.
26. Clarke MJ, Mulligan EA, Grogan PT, Mladek AC, Carlson BL, Schroeder MA, et al. Effective sensitization of temozolomide by ABT-888 is lost with development of temozolomide resistance in glioblastoma xenograft lines. Mol Cancer Ther 2009;8:407-14.
27. Gupta SK, Mladek AC, Carlson BL, Boakye-Agyeman F, Bakken KK, Kizilbash SH, et al. Discordant in vitro and in vivo chemopotentiating effects of the PARP inhibitor veliparib in temozolomide-sensitive versus-resistant glioblastoma multiforme xenografts. Clin Cancer Res 2014;20:3730-41.
28. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002;2:48-58.
29. Austin Doyle L, Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 2003;22:7340-58.
30. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene 2003;22:7468-85.
31. Murray J, ThomasH, Berry P, Kyle S, PattersonM, JonesC, et al. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer 2014;110:1977-84.
32. Kalpathy-Cramer J, Gerstner ER, Emblem KE, Andronesi OC, Rosen B. Advanced magnetic resonance imaging of the physical processes in human glioblastoma. Cancer Res 2014;74:4622-37.
33. Pafundi DH, Laack NN, Youland RS, Parney IF, Lowe VJ, Giannini C, et al. Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. Neuro-oncology 2013;15:1058-67.
34. Earnest FT, Kelly PJ, Scheithauer BW, Kall BA, Cascino TL, Ehman RL, et al. Cerebral astrocytomas: histopathologic correlation of MR and CT contrast enhancement with stereotactic biopsy. Radiology 1988;166:823-7.
35. Blakeley JO, Olson J, Grossman SA, He X, Weingart J, Supko JG. Effect of blood brain barrier permeability in recurrent high grade gliomas on the intratumoral pharmacokinetics of methotrexate: a microdialysis study. J Neurooncol 2009;91:51-8.
36. van Tellingen O, Yetkin-Arik B, de Gooijer MC, Wesseling P, Wurdinger T, de Vries HE. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat 2015;19:1-12.
37. Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res 2010;16:5664-78.
38. Schinkel AH, Jonker JW. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 2003;55: 3-29.
39. Agarwal S, Manchanda P, Vogelbaum MA, Ohlfest JR, Elmquist WF. Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells: findings in an orthotopic rat xenograft model of glioma. Drug Metab Dispos 2013;41:33-9.
40. Durmus S, Sparidans RW, van Esch A, Wagenaar E, Beijnen JH, Schinkel AH. Breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1) restrict oral availability and brain accumulation of the PARP inhibitor rucaparib (AG-014699). Pharm Res 2015;32:37-46.
41. Agarwal S, Sane R, Ohlfest JR, Elmquist WF. The role of the breast cancer resistance protein (ABCG2) in the distribution of sorafenib to the brain. J Pharmacol Exp Ther 2011;336:223-33.
42. Mittapalli RK, Vaidhyanathan S, Dudek AZ, Elmquist WF. Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther 2013;344:655-64.
43. Oberoi RK, Mittapalli RK, Elmquist WF. Pharmacokinetic assessment of efflux transport in sunitinib distribution to the brain. J Pharmacol Exp Ther 2013;347:755-64.
44. Chuan Tang S, Nguyen LN, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Int J Cancer 2014;134:1484-94.
45. Iusuf D, Teunissen SF, Wagenaar E, Rosing H, Beijnen JH, Schinkel AH. Pglycoprotein (ABCB1) transports the primary active tamoxifenmetabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration. J Pharmacol Exp Ther 2011;337:710-7.
46. Yung R, Seyfoddin V, Guise C, Tijono S, McGregor A, Connor B, et al. Efficacy against subcutaneous or intracranial murine GL261 gliomas in relation to the concentration of the vascular-disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), in the brain and plasma. Cancer Chemother Pharmacol 2014;73:639-49.
47. Pokorny JL, Calligaris D, Gupta SK, Iyekegbe DO, Mueller D, Bakken KK, et al. The efficacy of the Wee1 inhibitor MK-1775 combined with temozolomide is limited by heterogeneous distribution across the blood-brain barrier in glioblastoma. Clin Cancer Res 2015;21:1916-25.
48. Russo AL, Kwon HC, BurganWE, Carter D, Beam K,Weizheng X, et al. In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin Cancer Res 2009;15: 607-12.
49. Lawlor D, Martin P, Busschots S, Thery J, O'Leary JJ, Hennessy BT, et al. PARP inhibitors as p-glyoprotein substrates. J Pharm Sci 2014;103: 1913-20.
50. Chalmers A, Jackson A, Swaisland H, Stewart W, Halford S, Molife R, et al. Olaparib penetrates glioblastoma at therapeutic levels: results of stage 1 of the OPARATIC trial; a phase I study of olaparib in combination with temozolomide in patients with relapsed glioblastoma.J Clin Oncol 32:5s (suppl; abstr 2025).