Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer

Cancer Discovery

Volumn 2, Issue 11, 2012, Pages 1048-1063

  Juvekar, Ashish ^a   Burga, Laura N ^a   Hu, Hai ^a   Lunsford, Elaine P ^a   Ibrahim, Yasir H ^d   Balmañà, Judith ^d   Rajendran, Anbazhagan ^a   Papa, Antonella ^b   Spencer, Katherine ^a   Lyssiotis, Costas A ^b   Nardella, Caterina ^b   Pandolfi, Pier Paolo ^b   Baselga, José ^c,d   Scully, Ralph ^a   Asara, John M ^b   Cantley, Lewis C ^b   Wulf, Gerburg M ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 6 (1 THIANTHRENYL) 4 PYRANONE; BRCA1 PROTEIN; BUPARLISIB; FLUORODEOXYGLUCOSE F 18; GENOMIC DNA; HISTONE H2AX; MITOGEN ACTIVATED PROTEIN KINASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OLAPARIB; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAD51 PROTEIN; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ADENOSINE DIPHOSPHATE RIBOSYLATION; ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ARTICLE; BREAST CANCER; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; CORE BIOPSY NEEDLE; DNA DAMAGE; DRUG EFFICACY; FEMALE; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; MASS SPECTROMETRY; MOUSE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CELL LINE, TUMOR; DRUG SYNERGISM; ENZYME INHIBITORS; FEMALE; GENES, BRCA1; HUMANS; MICE; PHOSPHATIDYLINOSITOL 3-KINASES; POLY(ADP-RIBOSE) POLYMERASES;

EID: 84866709651     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-11-0336     Document Type: Article

References (50)

1. Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet 1995; 11: 428-433.
2. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proofof- concept trial. Lancet 2010; 376: 235-244.
3. 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: 123-134.
4. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. 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.
5. 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 platinumfree interval. J Clin Oncol 2010; 28: 2512-2519.
6. Collins LC, Martyniak A, Kandel MJ, Stadler ZK, Masciari S, Miron A, et al. Basal cytokeratin and epidermal growth factor receptor expression are not predictive of BRCA1 mutation status in women with triple-negative breast cancers. Am J Surg Pathol 2009; 33: 1093-1097.
7. van der Groep P, Bouter A, van der Zanden R, Siccama I, Menko FH, Gille JJ, et al. Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data. J Clin Pathol 2006; 59: 611-617.
8. Maor S, Yosepovich A, Papa MZ, Yarden RI, Mayer D, Friedman E, et al. Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutations. Cancer Lett 2007; 257: 236-243.
9. Neuhausen SL, Brummel S, Ding YC, Steele L, Nathanson KL, Domchek S, et al. Genetic variation in IGF2 and HTRA1 and breast cancer risk among BRCA1 and BRCA2 carriers. Cancer Epidemiol Biomarkers Prev 2011; 20: 1690-1702.
10. Neuhausen SL, Brummel S, Ding YC, Singer CF, Pfeiler G, Lynch HT, et al. Genetic variation in insulin-like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers. Breast Cancer Res 2009; 11: R76.
11. Burga LN, Hu H, Juvekar A, Tung NM, Troyan SL, Hofstatter EW, et al. Loss of BRCA1 leads to an increase in epidermal growth factor receptor expression in mammary epithelial cells, and epidermal growth factor receptor inhibition prevents estrogen receptor-negative cancers in BRCA1-mutant mice. Breast Cancer Res 2011; 13: R30.
12. Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, et al. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet 1999; 22: 37-43.
13. Brodie SG, Xu X, Qiao W, Li WM, Cao L, Deng CX. Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice. Oncogene 2001; 20: 7514-7523.
14. Shukla V, Coumoul X, Cao L, Wang RH, Xiao C, Xu X, et al. Absence of the full-length breast cancer-associated gene-1 leads to increased expression of insulin-like growth factor signaling axis members. Cancer Res 2006; 66: 7151-7157.
15. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A 2008; 105: 17079-17084.
16. Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell S N, et al. Negative regulation of AKT activation by BRCA1. Cancer Res 2008; 68: 10040-1004.
17. Razandi M, Pedram A, Rosen EM, Levin ER. BRCA1 inhibits membrane estrogen and growth factor receptor signaling to cell proliferation in breast cancer. Mol Cell Biol 2004; 24: 5900-5913.
18. Yan Y, Haas JP, Kim M, Sgagias MK, Cowan KH. BRCA1-induced apoptosis involves inactivation of ERK1/2 activities. J Biol Chem 2002; 277: 33422-3330.
19. Saal LH, Gruvberger-Saal SK, Persson C, Lovgren K, Jumppanen M, Staaf J, et al. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 2008; 40: 102-107.
20. Gewinner C, Wang ZC, Richardson A, Teruya-Feldstein J, Etemadmoghadam D, Bowtell D, et al. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell 2009; 16: 115-125.
21. Fedele CG, Ooms LM, Ho M, Vieusseux J, O'Toole SA, Millar EK, et al. Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers. Proc Natl Acad Sci U S A 2010; 107: 22231-22236.
22. Specht JM, Kurland BF, Montgomery SK, Dunnwald LK, Doot RK, Gralow JR, et al. Tumor metabolism and blood flow as assessed by positron emission tomography varies by tumor subtype in locally advanced breast cancer. Clin Cancer Res 2010; 16: 2803-2810.
23. Tafreshi NK, Kumar V, Morse DL, Gatenby RA. Molecular and functional imaging of breast cancer. Cancer Control 2010; 17: 143-155.
24. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008; 14: 1351-1356.
25. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006; 7: 606-619.
26. van der Heiden MG. Targeting cell metabolism in cancer patients. Sci Transl Med 2010; 2: 31ed1.
27. Schnell CR, Stauffer F, Allegrini PR, O'Reilly T, McSheehy PM, Dartois C, et al. Effects of the dual phosphatidylinositol 3-kinase/ mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res 2008; 68: 6598-6607.
28. Yuan TL, Choi HS, Matsui A, Benes C, Lifshits E, Luo J, et al. Class 1A PI3K regulates vessel integrity during development and tumorigenesis. Proc Natl Acad Sci U S A 2008; 105: 9739-9744.
29. Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL. Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 1995; 177: 275-283.
30. Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther 2012; 11: 317-328.
31. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011; 19: 58-71.
32. Tomlinson GE, Chen TT, Stastny VA, Virmani AK, Spillman MA, Tonk V, et al. Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier. Cancer Res 1998; 58: 3237-3242.
33. Forozan F, Veldman R, Ammerman CA, Parsa NZ, Kallioniemi A, Kallioniemi OP, et al. Molecular cytogenetic analysis of 11 new breast cancer cell lines. Br J Cancer 1999; 81: 1328-1334.
34. 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: 917-921.
35. Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM, Orr AI, et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 2004; 64: 9152-9159.
36. Drost R, Bouwman P, Rottenberg S, Boon U, Schut E, Klarenbeek S, et al. BRCA1 RING function is essential for tumor suppression but dispensable for therapy resistance. Cancer Cell 2011; 20: 797-809.
37. Yuan SS, Lee SY, Chen G, Song M, Tomlinson GE, Lee EY. BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res 1999; 59: 3547-3551.
38. Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 1998; 90: 1138-1145.
39. Kumar A, Fernandez-Capetillo O, Carrera AC. Nuclear phosphoinositide 3-kinase beta controls double-strand break DNA repair. Proc Natl Acad Sci U S A 2010; 107: 7491-746.
40. Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 2007; 128: 157-170.
41. Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem 2000; 275: 23899-23903.
42. Ha HC, Snyder SH. Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci U S A 1999; 96: 13978-13982.
43. Zingarelli B, Salzman AL, Szabo C. Genetic disruption of poly (ADPribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res 1998; 83: 85-94.
44. Eliasson MJ, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, et al. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 1997; 3: 1089-1095.
45. Soriano FG, Liaudet L, Szabo E, Virag L, Mabley JG, Pacher P, et al. Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase- 1-deficient mice. Shock 2002; 17: 286-292.
46. Masutani M, Suzuki H, Kamada N, Watanabe M, Ueda O, Nozaki T, et al. Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci U S A 1999; 96: 2301-2304.
47. Wagner KU, Wall RJ, St-Onge L, Gruss P, Wynshaw-Boris A, Garrett L, et al. Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res 1997; 25: 4323-4330.
48. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356: 215-221.
49. Fox SB, Turner GD, Leek RD, Whitehouse RM, Gatter KC, Harris AL. The prognostic value of quantitative angiogenesis in breast cancer and role of adhesion molecule expression in tumor endothelium. Breast Cancer Res Treat 1995; 36: 219-226.
50. Yuan M, Breitkopf SB, Yang X, Asara JM. A positive/negative ion-switching, targeted mass spectrometry-based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue. Nat Protoc 2012; 7: 872-881