Resistance acquisition to MDM2 inhibitors

Biochemical Society Transactions

Volumn 42, Issue 4, 2014, Pages 752-757

  Cinatl, Jindrich ^a   Speidel, Daniel ^b,c   Hardcastle, Ian ^d   Michaelis, Martin ^e  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^b CHILDREN'S MEDICAL RESEARCH INSTITUTE   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

^d NEWCASTLE UNIVERSITY   (United Kingdom)

^e UNIVERSITY OF KENT   (United Kingdom)

Author keywords

Acquired resistance; Murine double minute 2 inhibitor (MDM2 inhibitor); P53 mutation; Targeted therapy

Indexed keywords

ANTINEOPLASTIC AGENT; MDM2 INHIBITOR; PROTEIN MDM2; UNCLASSIFIED DRUG; PROTEIN P53;

CANCER CHEMOTHERAPY; CANCER RESISTANCE; CLINICAL EVALUATION; CLINICAL TRIAL (TOPIC); CONFERENCE PAPER; DNA DAMAGE; DRUG RESISTANCE; DRUG TARGETING; EXPERIMENTAL MODEL; GENE MUTATION; HUMAN; MEDICINAL CHEMISTRY; NONHUMAN; PRIORITY JOURNAL; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; METABOLISM; NEOPLASMS; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MDM2; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84905820972     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20140035     Document Type: Conference Paper

References (50)

1. Rebucci, M. and Michiels, C. (2013) Molecular aspects of cancer cell resistance to chemotherapy. Biochem. Pharmacol. 85, 1219-1226
2. Lee, A.J. and Swanton, C. (2012) Tumour heterogeneity and drug resistance: personalising cancer medicine through functional genomics. Biochem. Pharmacol. 83, 1013-1020
3. Chabner, B.A. and Roberts, Jr, T.G. (2005) Timeline: chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65-72
4. Yuan, Y., Liao, Y.M., Hsueh, C.T. and Mirshahidi, H.R. (2011) Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP. J. Hematol. Oncol. 4, 16
5. Lane, D.P. and Lain, S. (2002) Therapeutic exploitation of the p53 pathway. Trends Mol. Med. 8, S38-S42
6. Levine, A.J. and Oren, M. (2009) The first 30 years of p53: growing ever more complex. Nat. Rev. Cancer 9, 749-758
7. Brown, C.J., Cheok, C.F., Verma, C.S. and Lane, D.P. (2011) Reactivation of p53: from peptides to small molecules. Trends Pharmacol. Sci. 32, 53-62
8. Valentine, J.M., Kumar, S. and Moumen, A. (2011) A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation. BMC Cancer 11, 79
9. Rigatti, M.J., Verma, R., Belinsky, G.S., Rosenberg, D.W. and Giardina, C. (2012) Pharmacological inhibition of Mdm2 triggers growth arrest and promotes DNA breakage in mouse colon tumors and human colon cancer cells. Mol. Carcinog. 51, 363-378
10. Issaeva, N., Bozko, P., Enge, M., Protopopova, M., Verhoef, L.G., Masucci, M., Pramanik, A. and Selivanova, G. (2004) Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat. Med. 10, 1321-1328
11. Kussie, P.H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A.J. and Pavletich, N.P. (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948-953
12. Weber, L. (2010) Patented inhibitors of p53-Mdm2 interaction (2006-2008). Expert Opin. Ther. Pat. 20, 179-191
13. Zak, K., Pecak, A., Rys, B., Wladyka, B., Dömling, A., Weber, L., Holak, T. and Dubin, G. (2013) Mdm2 and MdmX inhibitors for the treatment of cancer: a patent review (2011-present). Expert Opin. Ther. Pat. 23, 425-448
14. Vassilev, L.T., Vu, B.T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C. et al. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844-848
15. Vu, B., Wovkulich, P., Pizzolato, G., Lovey, A., Ding, Q., Jiang, N., Liu, J.J., Zhao, C., Glenn, K., Wen, Y. et al. (2013) Discovery of RG7112: a small-molecule MDM2 inhibitor in clinical development. ACS Med. Chem. Lett. 4, 466-469
16. Zhao, Y., Liu, L., Sun, W., Lu, J., McEachern, D., Li, X., Yu, S., Bernard, D., Ochsenbein, P., Ferey, V. et al. (2013) Diastereomeric spirooxindoles as highly potent and efficacious MDM2 inhibitors. J. Am. Chem. Soc. 135, 7223-7234
17. Ding, Q., Zhang, Z., Liu, J.J., Jiang, N., Zhang, J., Ross, T.M., Chu, X.J., Bartkovitz, D., Podlaski, F., Janson, C. et al. (2013) Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J. Med. Chem. 56, 5979-5983
18. Hardcastle, I.R., Ahmed, S.U., Atkins, H., Calvert, A.H., Curtin, N.J., Farnie, G., Golding, B.T., Griffin, R.J., Guyenne, S., Hutton, C. et al. (2005) Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction. Bioorg. Med. Chem. Lett. 15, 1515-1520
19. Parks, D.J., LaFrance, L.V., Calvo, R.R., Milkiewicz, K.L., Gupta, V., Lattanze, J., Ramachandren, K., Carver, T.E., Petrella, E.C., Cummings, M.D. et al. (2005) 1,4-benzodiazepine-2,5-diones as small molecule antagonists of the HDM2-p53 interaction: discovery and SAR. Bioorg. Med. Chem. Lett. 15, 765-770
20. Allen, J.G., Bourbeau, M.P., Wohlhieter, G.E., Bartberger, M.D., Michelsen, K., Hungate, R., Gadwood, R.C., Gaston, R.D., Evans, B., Mann, L.W. et al. (2009) Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein interaction. J. Med. Chem. 52, 7044-7053
21. Furet, P., Chéne, P., De Pover, A., Valat, T.S., Lisztwan, J.H., Kallen, J. and Masuya, K. (2012) The central valine concept provides an entry in a new class of non peptide inhibitors of the p53-MDM2 interaction. Bioorg. Med. Chem. Lett. 22, 3498-3502
22. Rew, Y., Sun, D., Gonzalez-Lopez De Turiso, F., Bartberger, M.D., Beck, H.P., Canon, J., Chen, A., Chow, D., Deignan, J., Fox, B.M. et al. (2012) Structure-based design of novel inhibitors of the MDM2-p53 interaction. J. Med. Chem. 55, 4936-4954
23. Blackburn, T.J., Ahmed, S., Coxon, C.R., Liu, J., Lu, X., Golding, B.T., Griffin, R.J., Hutton, C., Newell, D.R., Ojo, S. et al. (2013) Diaryl- and triaryl-pyrrole derivatives: inhibitors of the MDM2-p53 and MDMX-p53 protein-protein interactions. MedChemComm 4, 1297-1304
24. Gonzalez-Lopez de Turiso, F., Sun, D., Rew, Y., Bartberger, M.D., Beck, H.P., Canon, J., Chen, A., Chow, D., Correll, T.L., Huang, X. et al. (2013) Rational design and binding mode duality of MDM2-p53 inhibitors. J. Med. Chem. 56, 4053-4070
25. Wang, W., Shangguan, S., Qiu, N., Hu, C., Zhang, L. and Hu, Y. (2013) Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 1. Bioorg. Med. Chem. 21, 2879-2885
26. Michaelis, M., Rothweiler, F., Klassert, D., von Deimling, A., Weber, K., Fehse, B., Kammerer, B., Doerr, H.W. and Cinatl, Jr, J. (2009) Reversal of P-glycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3. Cancer Res. 69, 416-421
27. Van Maerken, T., Ferdinande, L., Taildeman, J., Lambertz, I., Yigit, N., Vercruysse, L., Rihani, A., Michaelis, M., Cinatl, Jr, J., Cuvelier, C.A. et al. (2009) Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J. Natl. Cancer Inst. 101, 1562-1574
28. Saha, M.N., Qiu, L. and Chang, H. (2013) Targeting p53 by small molecules in hematological malignancies. J. Hematol. Oncol. 6, 23
29. Wade, M., Li, Y.C. and Wahl, G.M. (2013) MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat. Rev. Cancer 13, 83-96
30. Kranz, D. and Dobbelstein, M. (2006) Nongenotoxic p53 activation protects cells against S-phase-specific chemotherapy. Cancer Res. 66, 10274-10280
31. Stühmer, T., Chatterjee, M., Hildebrandt, M., Herrmann, P., Gollasch, H., Gerecke, C., Theurich, S., Cigliano, L., Manz, R.A., Daniel, P.T. et al. (2005) Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma. Blood 106, 3609-3617
32. Rao, B., Lain, S. and Thompson, A.M. (2013) p53-based cyclotherapy: exploiting the 'guardian of the genome' to protect normal cells from cytotoxic therapy. Br. J. Cancer 109, 2954-2958
33. Secchiero, P., Bosco, R., Celeghini, C. and Zauli, G. (2011) Recent advances in the therapeutic perspectives of Nutlin-3. Curr. Pharm. Des. 17, 569-577
34. Ambrosini, G., Sambol, E.B., Carvajal, D., Vassilev, L.T., Singer, S. and Schwartz, G.K. (2007) Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene 26, 3473-3481
35. Lau, L.M., Nugent, J.K., Zhao, X. and Irwin, M.S. (2008) HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function. Oncogene 27, 997-1003
36. Ha, J.H., Won, E.Y., Shin, J.S., Jang, M., Ryu, K.S., Bae, K.H., Park, S.G., Park, B.C., Yoon, H.S. and Chi, S.W. (2011) Molecular mimicry-based repositioning of nutlin-3 to anti-apoptotic Bcl-2 family proteins. J. Am. Chem. Soc. 133, 1244-1247
37. Zhang, F., Throm, S.L., Murley, L.L., Miller, L.A., Zatechka, Jr, D.S., Guy, K.R., Kennedy, R. and Stewart, C.F. (2011) MDM2 antagonist nutlin-3a reverses mitoxantrone resistance by inhibiting breast cancer resistance protein mediated drug transport. Biochem. Pharmacol. 82, 24-34
38. Tabernero, J., Dirix, L., Schöffski, P., Cervantes, A., Lopez-Martin, J.A., Capdevila, J., van Beijsterveldt, L., Platero, S., Hall, B., Yuan, Z. et al. (2011) A phase I first-in-human pharmacokinetic and pharmacodynamic study of serdemetan in patients with advanced solid tumors. Clin. Cancer Res. 17, 6313-6321
39. Ray-Coquard, I., Blay, J.Y., Italiano, A., Le Cesne, A., Penel, N., Zhi, J., Heil, F., Rueger, R., Graves, B., Ding, M. et al. (2012) Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol. 13, 1133-1140
40. Smith, M.A., Gorlick, R., Kolb, E.A., Lock, R., Carol, H., Maris, J.M., Keir, S.T., Morton, C.L., Reynolds, C.P., Kang, M.H. et al. (2012) Initial testing of JNJ-26854165 (Serdemetan) by the pediatric preclinical testing program. Pediatr. Blood Cancer 59, 329-332
41. Shen, H., Moran, D.M. and Maki, C.G. (2008) Transient nutlin-3a treatment promotes endoreduplication and the generation of therapy-resistant tetraploid cells. Cancer Res. 68, 8260-8268
42. Michaelis, M., Rothweiler, F., Barth, S., Cinatl, J., van Rikxoort, M., Löschmann, N., Voges, Y., Breitling, R., von Deimling, A., Rödel, F. et al. (2011) Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells. Cell Death Dis. 2, e243
43. Wei, S.J., Joseph, T., Sim, A.Y., Yurlova, L., Zolghadr, K., Lane, D., Verma, C. and Ghadessy, F. (2013) In vitro selection of mutant HDM2 resistant to Nutlin inhibition. PLoS ONE 8, e62564
44. Aziz, M.H., Shen, H. and Maki, C.G. (2011) Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3. Oncogene 30, 4678-4686
45. Jones, R.J., Bjorklund, C.C., Baladandayuthapani, V., Kuhn, D.J. and Orlowski, R.Z. (2012) Drug resistance to inhibitors of the human double minute-2 E3 ligase is mediated by point mutations of p53, but can be overcome with the p53 targeting agent RITA. Mol. Cancer Ther. 11, 2243-2253
46. Michaelis, M., Rothweiler, F., Agha, B., Barth, S., Voges, Y., Löschmann, N., von Deimling, A., Breitling, R., Doerr, H.W., Rödel, F. et al. (2012) Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents. Cell Death Dis. 3, e294
47. Chen, L. and Tweddle, D.A. (2012) p53, SKP2, and DKK3 as MYCN target genes and their potential therapeutic significance. Front. Oncol. 2, 173
48. Yang, J., Ahmed, A., Poon, E., Perusinghe, N., de Haven Brandon, A., Box, G., Valenti, M., Eccles, S., Rouschop, K. et al. (2009) Small-molecule activation of p53 blocks hypoxia-inducible factor 1 and vascular endothelial growth factor expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia. Mol. Cell. Biol. 29, 2243-2253
49. Melo, A.N. and Eischen, C.M. (2012) Protecting the genome from Mdm2 and Mdmx. Genes Cancer 3, 283-290
50. Lackner, M.R., Wilson, T.R. and Settleman, J. (2012) Mechanisms of acquired resistance to targeted cancer therapies. Future Oncol. 8, 999-1014