Mechanistic rationale to target PTEN-deficient tumor cells with inhibitors of the DNA damage response kinase ATM

Cancer Research

Volumn 75, Issue 11, 2015, Pages 2159-2165

  McCabe, Nuala ^a,b   Hanna, Conor ^a   Walker, Steven M ^a,b   Gonda, David ^c   Li, Jie ^c   Wikstrom, Katarina ^b   Savage, Kienan I ^a   Butterworth, Karl T ^a   Chen, Clark ^c   Harkin, D Paul ^a,b   Prise, Kevin M ^a   Kennedy, Richard D ^a,b  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^b Almac Sciences   (United Kingdom)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 6 (1 THIANTHRENYL) 4 PYRANONE; ATM PROTEIN; KU 60019; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN SERINE THREONINE KINASE INHIBITOR; REACTIVE OXYGEN METABOLITE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; 2-(2,6-DIMETHYLMORPHOLIN-4-YL)-N-(5-(6-MORPHOLIN-4-YL-4-OXO-4H-PYRAN-2-YL)-9H-THIOXANTHEN-2-YL)ACETAMIDE; ATM PROTEIN, HUMAN; MORPHOLINE DERIVATIVE; PTEN PROTEIN, HUMAN; THIOXANTHENE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL LINE; CANCER INHIBITION; CELL CYCLE ARREST; CELL DEATH; CHROMOSOME ABERRATION; CONTROLLED STUDY; DNA DAMAGE; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG MECHANISM; DRUG SENSITIVITY; DRUG SPECIFICITY; DRUG TARGETING; ENZYME ACTIVATION; FIBROBLAST; GENE SILENCING; GLIOBLASTOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; MUTANT; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROSTATE CANCER; TUMOR XENOGRAFT; WILD TYPE; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; COLORECTAL NEOPLASMS; DNA REPAIR; DRUG EFFECTS; GENETICS; HCT116 CELL LINE; MITOSIS; PATHOLOGY; XENOGRAFT;

ANIMALS; APOPTOSIS; ATAXIA TELANGIECTASIA MUTATED PROTEINS; COLORECTAL NEOPLASMS; DNA DAMAGE; DNA REPAIR; HCT116 CELLS; HETEROGRAFTS; HUMANS; MICE; MITOSIS; MORPHOLINES; PTEN PHOSPHOHYDROLASE; RNA, SMALL INTERFERING; THIOXANTHENES;

EID: 84939451678     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-14-3502     Document Type: Article

References (20)

1. Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol 2013; 14: 197-210.
2. Hickson I, Zhao Y, Richardson C.J., 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: 9152-59.
3. Batey MA, Zhao Y, Kyle S., Richardson C, Slade A, Martin N.M., et al. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther 2013; 12: 959-67.
4. Lord CJ, Ashworth A. Targeted therapy for cancer using PARP inhibitors. Curr Opin Pharmacol 2008; 8: 363-9.
5. Kennedy RD, Chen CC, Stuckert P, Archila E.M., De la Vega MA, Moreau LA, et al. Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. J Clin Invest 2007; 117:1440-9.
6. Lee C, Kim JS, Waldman T. PTEN gene targeting revealsaradiation-induced size checkpoint in human cancer cells. Cancer Res 2004; 64: 6906-14.
7. Maxwell PJ, Coulter J, Walker S.M., McKechnie M., Neisen J, McCabe N, et al. Potentiation of inflammatory CXCL8 signaling sustains cell survival in PTEN-deficient prostate carcinoma. Eur Urol 2013; 64: 177-88.
8. Ziv Y, Bar-Shira A, Pecker I., Russell P, Jorgensen TJ, Tsarfati I, et al Recombinant ATM protein complements the cellular A-T phenotype. Oncogene 1997; 15: 159-67.
9. 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: 157-70.
10. Gupta A, Yang Q, Pandita R.K., Hunt CR, Xiang T, Misri S, et al Cell cycle checkpoint defects contribute to genomic instability in PTEN-deficient cells independent of DNA DSB repair. Cell Cycle 2009; 8: 2198-210.
11. McEllin B, Camacho CV, Mukherjee B, Hahm B., Tomimatsu N, Bachoo RM, et al PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res 2010; 70: 5457-64.
12. Li J, Yen C, Liaw D., Podsypanina K, Bose S, Wang S.I., et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275: 1943-47.
13. Mendes-Pereira A.M., Martin SA, Brough R, McCarthy A., Taylor JR, Kim JS, et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 2009; 1: 315-22.
14. Fraser M, Zhao H, Luoto K.R., Lundin C., Coackley CL, Chan N, et al. PTEN deletion in prostate cancer cells does not associate with loss of RAD51 function: implications for radiotherapy and chemotherapy. Clin Cancer Res 2012; 18: 1025-27.
15. Huo YY, Li G, Duan R.F., Gou Q., Fu CL, Hu YC, et al. PTEN deletion leads to deregulation of antioxidants and increased oxidative damage in mouse embryonic fibroblasts. Free Radic Biol Med 2008; 44: 1578-91.
16. Harper JV, Anderson JA, O'Neill P. Radiation induced DNA DSBs: Contribution from stalled replication forks? DNA Repair 2010; 9: 907-13.
17. Golding SE, Rosenberg E, Valerie N., Hussaini I, Frigerio M, Cockcroft X.F., et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther 2009; 8: 2894-902.
18. Manning BD, Cantley LC AKT/PKB signaling: navigating downstream. Cell 2007; 129: 1261-74.
19. Bassi C, Ho J, Srikumar T., Dowling RJ, Gorrini C, Miller SJ, et al Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science 2013; 341: 395-9.
20. Bartkova J, Rezaei N, Liontos M., Karakaidos P, Kletsas D, Issaeva N., et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006; 444: 633-7.