Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment

Nature

Volumn 523, Issue 7560, 2015, Pages 352-356

  Alexandrova, E M ^a   Yallowitz, A R ^a   Li, D ^a   Xu, S ^a   Schulz, R ^b   Proia, D A ^c   Lozano, G ^d   Dobbelstein, M ^b   Moll, U M ^a,b  

^a STONY BROOK UNIVERSITY   (United States)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c Synta Pharmaceuticals Corp   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALVESPIMYCIN; GANETESPIB; HEAT SHOCK PROTEIN 90; PROTEIN P53; TAMOXIFEN; VORINOSTAT; HDAC6 PROTEIN, MOUSE; HISTONE DEACETYLASE; MUTANT PROTEIN; TRIAZOLE DERIVATIVE;

APOPTOSIS; GENE EXPRESSION; GROWTH RATE; MUTATION; PROTEIN; RODENT; SURVIVAL; TUMOR;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL; CARCINOGENESIS; CARCINOGENICITY; CONTROLLED STUDY; DRUG ACTIVITY; DRUG TARGETING; FEMALE; HUMAN; HUMAN CELL; MALE; MISSENSE MUTATION; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARIAN CANCER CELL LINE; PRIORITY JOURNAL; PROSTATE CANCER; T CELL LYMPHOMA; TUMOR REGRESSION; ALLOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CANCER TRANSPLANTATION; DISEASE MODEL; DRUG EFFECTS; GENETICS; LYMPHOMA; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PROCEDURES; PROTEIN STABILITY; SURVIVAL RATE; TUMOR CELL LINE;

ANIMALIA; MUS;

ALLELES; ALLOGRAFTS; ANIMALS; APOPTOSIS; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; FEMALE; HISTONE DEACETYLASES; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LYMPHOMA; MALE; MICE; MOLECULAR TARGETED THERAPY; MUTANT PROTEINS; NEOPLASM TRANSPLANTATION; PROTEIN STABILITY; SURVIVAL RATE; TAMOXIFEN; TRIAZOLES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84937604711     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature14430     Document Type: Article

References (36)

1. Doyle, B. et al. p53 mutation and loss have different effects on tumourigenesis in a novel mouse modelof pleomorphic rhabdomyosarcoma. J. Pathol. 222, 129-137 (2010).
2. Hanel, W. et al. Two hot spot mutant p53 mouse models display differentialgain of function in tumorigenesis. Cell Death Differ. 20, 898-909 (2013).
3. Lang, G.A. et al. Gainoffunctionofap53 hot spot mutationinamousemodelofLi-Fraumeni syndrome. Cell 119, 861-872 (2004).
4. Morton, J. P. et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc. Natl Acad. Sci. USA 107, 246-251 (2010).
5. Olive, K. P.et al. Mutant p53 gain of functionin two mouse models of Li-Fraumeni syndrome. Cell 119, 847-860 (2004).
6. Brosh, R. & Rotter, V. When mutants gain new powers: news from the mutant p53 field. Nature Rev. Cancer 9, 701-713 (2009).
7. Terzian, T. et al. The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss. Genes Dev. 22, 1337-1344 (2008).
8. Suh, Y. A. et al. Multiple stress signals activate mutant p53 in vivo. Cancer Res. 71, 7168-7175 (2011).
9. Blagosklonny, M. V., Toretsky, J., Bohen, S. & Neckers, L. Mutant conformation of p53 translatedinvitroorinvivo requires functional HSP90. Proc. Natl Acad. Sci. USA 93, 8379-8383 (1996).
10. Whitesell, L., Sutphin, P. D., Pulcini, E. J., Martinez, J. D. & Cook, P. H. The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent. Mol. Cell. Biol. 18, 1517-1524 (1998).
11. Li, D., Marchenko, N. D. & Moll, U. M. SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis. Cell Death Differ. 18, 1904-1913 (2011).
12. Li, D. et al. Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol. Cancer Res. 9, 577-588 (2011).
13. Bougeard, G. et al. Molecular basis of the Li-Fraumeni syndrome: anupdate from the French LFS families. J. Med. Genet. 45, 535-538 (2008).
14. Zerdoumi, Y. et al. Drastic effect of germline TP53 missense mutations in Li-Fraumeni patients. Hum. Mutat. 34, 453-461 (2013).
15. Muller, P.A. & Vousden, K.H. Mutant p53incancer: new functions and therapeutic opportunities. Cancer Cell 25, 304-317 (2014).
16. Weissmueller, S. et al. Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor beta signaling. Cell 157, 382-394 (2014).
17. Trepel, J., Mollapour, M., Giaccone, G. & Neckers, L. Targeting the dynamic HSP90 complex in cancer. Nature Rev. Cancer 10, 537-549 (2010).
18. Whitesell, L. & Lindquist, S. L. HSP90 and the chaperoning of cancer. Nature Rev. Cancer 5, 761-772 (2005).
19. Dai, C., Whitesell, L., Rogers, A. B. & Lindquist, S. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130, 1005-1018 (2007).
20. Min, J. N., Huang, L., Zimonjic, D. B., Moskophidis, D. & Mivechi, N. F. Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumors. Oncogene 26, 5086-5097 (2007).
21. Slingerland, M., Guchelaar, H. J. & Gelderblom, H. Histone deacetylase inhibitors: an overview of the clinical studies in solid tumors. Anticancer Drugs 25, 140-149 (2014).
22. Zou, J., Guo, Y., Guettouche, T., Smith, D. F. & Voellmy, R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94, 471-480 (1998).
23. Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603-607 (2012).
24. Siegel, D., Yan, C. & Ross, D. NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. Biochem. Pharmacol. 83, 1033-1040 (2012).
25. Proia, D. A. & Bates, R. C. Ganetespib and HSP90: translating preclinical hypotheses into clinical promise. Cancer Res. 74, 1294-1300 (2014).
26. Socinski, M. A. et al. A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clin. Cancer Res. 19, 3068-3077 (2013).
27. Harvey, M. et al. Genetic background alters the spectrumoftumors that develop in p53-deficient mice. FASEB J. 7, 938-943 (1993).
28. Jacks, T. et al. Tumor spectrum analysis in p53-mutant mice. Curr. Biol. 4, 1-7 (1994).
29. Landmann, H. et al. UDP glucuronosyltransferase 1A expression levels determine the response of colorectal cancer cells to the heat shock protein 90 inhibitor ganetespib. Cell Death Dis. 5, e1411 (2014).
30. Khoo, K. H., Verma, C. S. & Lane, D. P. Drugging the p53 pathway: understanding the route to clinical efficacy. Nature Rev. Drug Discov. 13, 217-236 (2014).
31. Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661-665 (2007).
32. Dobbelstein, M. & Moll, U. Targeting tumour-supportive cellular machineries in anticancer drug development. Nature Rev. Drug Discov. 13, 179-196 (2014).
33. Gorska, M.et al. Geldanamycin and its derivativesas Hsp90 inhibitors. Front. Biosci. 17, 2269-2277 (2012).
34. Hrzenjak, A. et al. Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo. Mol. Cancer 9, 49 (2010).
35. Proia, D.A.et al. Multifaceted intervention by the Hsp90 inhibitor ganetespib (STA-9090) in cancer cells with activated JAK/STAT signaling. PLoS ONE 6, e18552 (2011).
36. Ying, W.et al. Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol. Cancer Ther. 11, 475-484 (2012).