Mutant p53 reactivation by small molecules makes its way to the clinic

FEBS Letters

Volumn 588, Issue 16, 2014, Pages 2622-2627

  Bykov, Vladimir J N ^a   Wiman, Klas G ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Cancer; Cell death; Clinical trial; Drug discovery; Mutation; p53

Indexed keywords

3 DEAZANEPLANOCIN A; 4 (3 DIMETHYLAMINOPROPYLAMINO) 2 (4 METHOXYSTYRYL)QUINAZOLINE; ANTINEOPLASTIC AGENT; APR 246; DAUNORUBICIN; DOXORUBICIN; MIRA 1; MOLECULAR THERAPY AGENT; NSC 319726; PK 083; PK 5174; PK 7088; PRIMA 1; PROTEIN P53; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL (TOPIC); DRUG BINDING; DRUG DESIGN; DRUG MECHANISM; DRUG POTENTIATION; DRUG RESPONSE; DRUG SAFETY; DRUG TARGETING; HEMATOLOGIC MALIGNANCY; HUMAN; MOLECULARLY TARGETED THERAPY; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; TREATMENT OUTCOME;

CANCER; CELL DEATH; CLINICAL TRIAL; DRUG DISCOVERY; MUTATION; P53;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASMS; SMALL MOLECULE LIBRARIES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84905124070     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1016/j.febslet.2014.04.017     Document Type: Review

References (54)

1. K.H. Vousden, and C. Prives Blinded by the light: the growing complexity of p53 Cell 137 2009 413 431
2. J. Bartkova, Z. Horejsi, K. Koed, A. Kramer, F. Tort, K. Zieger, P. Guldberg, M. Sehested, J.M. Nesland, C. Lukas, T. Orntoft, J. Lukas, and J. Bartek DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis Nature 434 2005 864 870
3. V.G. Gorgoulis, L.V. Vassiliou, P. Karakaidos, P. Zacharatos, A. Kotsinas, T. Liloglou, M. Venere, R.A. Ditullio Jr.; N.G. Kastrinakis, B. Levy, D. Kletsas, A. Yoneta, M. Herlyn, C. Kittas, and T.D. Halazonetis Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions Nature 434 2005 907 913
4. T. Soussi, and K.G. Wiman Shaping genetic alterations in human cancer: the p53 mutation paradigm Cancer Cell 12 2007 303 312
5. P.A. Muller, and K.H. Vousden Mutant p53 in cancer: new functions and therapeutic opportunities Cancer Cell 25 2014 304 317
6. R. Brosh, and V. Rotter When mutants gain new powers: news from the mutant p53 field Nat. Rev. Cancer 9 2009 701 713
7. K.P. Olive, D.A. Tuveson, Z.C. Ruhe, B. Yin, N.A. Willis, R.T. Bronson, D. Crowley, and T. Jacks Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome Cell 119 2004 847 860
8. G.A. Lang, T. Iwakuma, Y.A. Suh, G. Liu, V.A. Rao, J.M. Parant, Y.A. Valentin-Vega, T. Terzian, L.C. Caldwell, L.C. Strong, A.K. El-Naggar, and G. Lozano Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome Cell 119 2004 861 872
9. J.P. Morton, P. Timpson, S.A. Karim, R.A. Ridgway, D. Athineos, B. Doyle, N.B. Jamieson, K.A. Oien, A.M. Lowy, V.G. Brunton, M.C. Frame, T.R. Evans, and O.J. Sansom Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer Proc. Natl. Acad. Sci. USA 107 2010 246 251
10. C. Gaiddon, M. Lokshin, J. Ahn, T. Zhang, and C. Prives A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain Mol. Cell. Biol. 21 2001 1874 1887
11. P.A. Muller, P.T. Caswell, B. Doyle, M.P. Iwanicki, E.H. Tan, S. Karim, N. Lukashchuk, D.A. Gillespie, R.L. Ludwig, P. Gosselin, A. Cromer, J.S. Brugge, O.J. Sansom, J.C. Norman, and K.H. Vousden Mutant p53 drives invasion by promoting integrin recycling Cell 139 2009 1327 1341
12. D. Hanahan, and R.A. Weinberg The hallmarks of cancer Cell 100 2000 57 70
13. D. Hanahan, and R.A. Weinberg Hallmarks of cancer: the next generation Cell 144 2011 646 674
14. C.P. Martins, L. Brown-Swigart, and G.I. Evan Modeling the therapeutic efficacy of p53 restoration in tumors Cell 127 2006 1323 1334
15. A. Ventura, D.G. Kirsch, M.E. McLaughlin, D.A. Tuveson, J. Grimm, L. Lintault, J. Newman, E.E. Reczek, R. Weissleder, and T. Jacks Restoration of p53 function leads to tumour regression in vivo Nature 445 2007 661 665
16. W. Xue, L. Zender, C. Miething, R.A. Dickins, E. Hernando, V. Krizhanovsky, C. Cordon-Cardo, and S.W. Lowe Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas Nature 445 2007 656 660
17. F.M. Boeckler, A.C. Joerger, G. Jaggi, T.J. Rutherford, D.B. Veprintsev, and A.R. Fersht Targeted rescue of a destabilized mutant of p53 by an in silico screened drug Proc. Natl. Acad. Sci. USA 105 2008 10360 10365
18. X. Liu, R. Wilcken, A.C. Joerger, I.S. Chuckowree, J. Amin, J. Spencer, and A.R. Fersht Small molecule induced reactivation of mutant p53 in cancer cells Nucleic Acids Res. 41 2013 6034 6044
19. V.J. Bykov, N. Issaeva, A. Shilov, M. Hultcrantz, E. Pugacheva, P. Chumakov, J. Bergman, K.G. Wiman, and G. Selivanova Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound Nat. Med. 8 2002 282 288
20. V.J. Bykov, N. Issaeva, N. Zache, A. Shilov, M. Hultcrantz, J. Bergman, G. Selivanova, and K.G. Wiman Reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs J. Biol. Chem. 280 2005 30384 30391
21. J.M. Lambert, P. Gorzov, D.B. Veprintsev, M. Soderqvist, D. Segerback, J. Bergman, A.R. Fersht, P. Hainaut, K.G. Wiman, and V.J. Bykov PRIMA-1 reactivates mutant p53 by covalent binding to the core domain Cancer Cell 15 2009 376 388
22. R. Zandi, G. Selivanova, C.L. Christensen, T.A. Gerds, B.M. Willumsen, and H.S. Poulsen PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53 Clin. Cancer Res. 17 2011 2830 2841
23. M.N. Saha, H. Jiang, Y. Yang, D. Reece, and H. Chang PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa Mol. Cancer Ther. 12 2013 2331 2341
24. W. Bao, M. Chen, X. Zhao, R. Kumar, C. Spinnler, M. Thullberg, N. Issaeva, G. Selivanova, and S. Stromblad PRIMA-1Met/APR-246 induces wild-type p53-dependent suppression of malignant melanoma tumor growth in 3D culture and in vivo Cell Cycle 10 2011 301 307
25. D. Ali, K. Jonsson-Videsater, S. Deneberg, S. Bengtzen, H. Nahi, C. Paul, and S. Lehmann APR-246 exhibits anti-leukemic activity and synergism with conventional chemotherapeutic drugs in acute myeloid leukemia cells Eur. J. Haematol. 86 2011 206 215
26. D.N. Aryee, S. Niedan, J. Ban, R. Schwentner, K. Muehlbacher, M. Kauer, R. Kofler, and H. Kovar Variability in functional p53 reactivation by PRIMA-1(Met)/APR-246 in Ewing sarcoma Br. J. Cancer 109 2013 2696 2704
27. C.V. Rao, J.M. Patlolla, L. Qian, Y. Zhang, M. Brewer, A. Mohammed, D. Desai, S. Amin, S. Lightfoot, and L. Kopelovich Chemopreventive effects of the p53-modulating agents CP-31398 and Prima-1 in tobacco carcinogen-induced lung tumorigenesis in A/J mice Neoplasia 15 2013 1018 1027
28. X. Peng, M.Q. Zhang, F. Conserva, G. Hosny, G. Selivanova, V.J. Bykov, E.S. Arner, and K.G. Wiman APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase Cell Death Dis. 4 2013 e881
29. M. Rieber, and M. Strasberg-Rieber Hypoxia, Mn-SOD and H(2)O(2) regulate p53 reactivation and PRIMA-1 toxicity irrespective of p53 status in human breast cancer cells Biochem. Pharmacol. 84 2012 1563 1570
30. H. Schmale, and C. Bamberger A novel protein with strong homology to the tumor suppressor p53 Oncogene 15 1997 1363 1367
31. N. Rokaeus, J. Shen, I. Eckhardt, V.J. Bykov, K.G. Wiman, and M.T. Wilhelm PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73 Oncogene 29 2010 6442 6451
32. J. Shen, E.H. van den Bogaard, E.N. Kouwenhoven, V.J. Bykov, T. Rinne, Q. Zhang, G.S. Tjabringa, C. Gilissen, S.J. van Heeringen, J. Schalkwijk, H. van Bokhoven, K.G. Wiman, and H. Zhou APR-246/PRIMA-1(MET) rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations Proc. Natl. Acad. Sci. USA 110 2013 2157 2162
33. R. Shalom-Feuerstein, L. Serror, E. Aberdam, F.J. Muller, H. van Bokhoven, K.G. Wiman, H. Zhou, D. Aberdam, and I. Petit Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET Proc. Natl. Acad. Sci. USA 110 2013 2152 2156
34. J.L. Kaar, N. Basse, A.C. Joerger, E. Stephens, T.J. Rutherford, and A.R. Fersht Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding Protein Sci. 19 2010 2267 2278
35. J. Scotcher, D.J. Clarke, S.K. Weidt, C.L. Mackay, T.R. Hupp, P.J. Sadler, and P.R. Langridge-Smith Identification of two reactive cysteine residues in the tumor suppressor protein p53 using top-down FTICR mass spectrometry J. Am. Soc. Mass Spectrom. 22 2011 888 897
36. B.A. Foster, H.A. Coffey, M.J. Morin, and F. Rastinejad Pharmacological rescue of mutant p53 conformation and function Science 286 1999 2507 2510
37. V. Madka, Y. Zhang, Q. Li, A. Mohammed, P. Sindhwani, S. Lightfoot, X.R. Wu, L. Kopelovich, and C.V. Rao P53-stabilizing agent CP-31398 prevents growth and invasion of urothelial cancer of the bladder in transgenic UPII-SV40T mice Neoplasia 15 2013 966 974
38. W. Wang, R. Takimoto, F. Rastinejad, and W.S. El-Deiry Stabilization of p53 by CP-31398 inhibits ubiquitination without altering phosphorylation at serine 15 or 20 or MDM2 binding Mol. Cell. Biol. 23 2003 2171 2181
39. T.M. Rippin, V.J. Bykov, S.M. Freund, G. Selivanova, K.G. Wiman, and A.R. Fersht Characterization of the p53-rescue drug CP-31398 in vitro and in living cells Oncogene 21 2002 2119 2129
40. N. Zache, J.M. Lambert, N. Rokaeus, J. Shen, P. Hainaut, J. Bergman, K.G. Wiman, and V.J. Bykov Mutant p53 targeting by the low molecular weight compound STIMA-1 Mol. Oncol. 2 2008 70 80
41. M. Demma, E. Maxwell, R. Ramos, L. Liang, C. Li, D. Hesk, R. Rossman, A. Mallams, R. Doll, M. Liu, C. Seidel-Dugan, W.R. Bishop, and B. Dasmahapatra SCH529074, a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth-suppressive function to mutant p53 and interrupts HDM2-mediated ubiquitination of wild type p53 J. Biol. Chem. 285 2010 10198 10212
42. L.M. Shi, Y. Fan, T.G. Myers, P.M. O'Connor, K.D. Paull, S.H. Friend, and J.N. Weinstein Mining the NCI anticancer drug discovery databases: genetic function approximation for the QSAR study of anticancer ellipticine analogues J. Chem. Inf. Comput. Sci. 38 1998 189 199
43. L. Weinmann, J. Wischhusen, M.J. Demma, U. Naumann, P. Roth, B. Dasmahapatra, and M. Weller A novel p53 rescue compound induces p53-dependent growth arrest and sensitises glioma cells to Apo2L/TRAIL-induced apoptosis Cell Death Differ. 15 2008 718 729
44. C.D. Wassman, R. Baronio, O. Demir, B.D. Wallentine, C.K. Chen, L.V. Hall, F. Salehi, D.W. Lin, B.P. Chung, G.W. Hatfield, A. Richard Chamberlin, H. Luecke, R.H. Lathrop, P. Kaiser, and R.E. Amaro Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53 Nat. Commun. 4 2013 1407
45. T.E. Baroni, T. Wang, H. Qian, L.R. Dearth, L.N. Truong, J. Zeng, A.E. Denes, S.W. Chen, and R.K. Brachmann A global suppressor motif for p53 cancer mutants Proc. Natl. Acad. Sci. USA 101 2004 4930 4935
46. R.K. Brachmann, K. Yu, Y. Eby, N.P. Pavletich, and J.D. Boeke Genetic selection of intragenic suppressor mutations that reverse the effect of common p53 cancer mutations EMBO J. 17 1998 1847 1859
47. X. Yu, A. Vazquez, A.J. Levine, and D.R. Carpizo Allele-specific p53 mutant reactivation Cancer Cell 21 2012 614 625
48. K.K. Hoe, C.S. Verma, and D.P. Lane Drugging the p53 pathway: understanding the route to clinical efficacy Nat. Rev. Drug Discovery 13 2014 217 236
49. J.E. Kravchenko, G.V. Ilyinskaya, P.G. Komarov, L.S. Agapova, D.V. Kochetkov, E. Strom, E.I. Frolova, I. Kovriga, A.V. Gudkov, E. Feinstein, and P.M. Chumakov Small-molecule RETRA suppresses mutant p53-bearing cancer cells through a p73-dependent salvage pathway Proc. Natl. Acad. Sci. USA 105 2008 6302 6307
50. V.J. Bykov, N. Zache, H. Stridh, J. Westman, J. Bergman, G. Selivanova, and K.G. Wiman PRIMA-1(MET) synergizes with cisplatin to induce tumor cell apoptosis Oncogene 24 2005 3484 3491
51. B. Cui, Q. Yang, H. Guan, B. Shi, P. Hou, and M. Ji PRIMA-1, a mutant p53 reactivator, restores the sensitivity of TP53 mutant-type thyroid cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep) J. Clin. Endocrinol. Metab. 2014 jc20133147
52. C. Floquet, J. Deforges, J.P. Rousset, and L. Bidou Rescue of non-sense mutated p53 tumor suppressor gene by aminoglycosides Nucleic Acids Res. 39 2011 3350 3362
53. L. Martin, A. Grigoryan, D. Wang, J. Wang, L. Breda, S. Rivella, T. Cardozo, and L.B. Gardner Identification and characterization of small molecules that inhibit nonsense mediated RNA decay and suppress nonsense p53 mutations Cancer Res. 2014 10.1158/0008-5472.CAN-13-2235 (Epub ahead of print)
54. S. Lehmann, V.J. Bykov, D. Ali, O. Andren, H. Cherif, U. Tidefelt, B. Uggla, J. Yachnin, G. Juliusson, A. Moshfegh, C. Paul, K.G. Wiman, and P.O. Andersson Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer J. Clin. Oncol. 30 2012 3633 3639