Proteasome-associated deubiquitinases and cancer

Cancer and Metastasis Reviews

Volumn 36, Issue 4, 2017, Pages 635-653

  Mofers, Arjan ^a   Pellegrini, Paola ^a   Linder, Stig ^a,b   D’Arcy, Pádraig ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Cancer; Deubiquitinases; Proteasome; Ubiquitin

Indexed keywords

19S REGULATORY PARTICLE; 20S CORE PARTICLE; ANTINEOPLASTIC AGENT; B AP 15; BETULIC ACID; BORTEZOMIB; CAPZIMIN; CARFILZOMIB; DEUBIQUITINASE; DNA; EOAI 3402143; IXAZOMIB; LIGASE INHIBITOR; ONCOPROTEIN; OPROZOMIB; P 5091; PROTEASOME; PROTEASOME INHIBITOR; PYR 41; PYZD 4409; REGULATOR PROTEIN; UBIQUITIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; USP 8I; VLX 1570; WP 1130;

ARTICLE; CANCER RESISTANCE; CARCINOGENESIS; CYTOTOXICITY; DNA REPAIR; HUMAN; MALIGNANT NEOPLASM; MANTLE CELL LYMPHOMA; MULTIPLE MYELOMA; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; UBIQUITINATION; ANIMAL; ANTAGONISTS AND INHIBITORS; ENZYMOLOGY; METABOLISM; NEOPLASM;

ANIMALS; DEUBIQUITINATING ENZYMES; HUMANS; NEOPLASMS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEASOME INHIBITORS;

EID: 85033593401     PISSN: 01677659     EISSN: 15737233     Source Type: Journal    
DOI: 10.1007/s10555-017-9697-6     Document Type: Article

References (138)

1. Herrmann, J., Ciechanover, A., Lerman, L. O., & Lerman, A. (2004). The ubiquitin-proteasome system in cardiovascular diseases—a hypothesis extended. Cardiovascular Research, 61(1), 11–21.
2. Lehman, N. L. (2009). The ubiquitin proteasome system in neuropathology. Acta Neuropathologica, 118(3), 329–347. https://doi.org/10.1007/s00401-009-0560-x.
3. Li, W., Bengtson, M. H., Ulbrich, A., Matsuda, A., Reddy, V. A., Orth, A., et al. (2008). Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One, 3(1), e1487. https://doi.org/10.1371/journal.pone.0001487.
4. Komander, D. (2009). The emerging complexity of protein ubiquitination. Biochemical Society Transactions, 37(Pt 5), 937–953. https://doi.org/10.1042/BST0370937.
5. Peterson, L. F., Sun, H., Liu, Y., Potu, H., Kandarpa, M., Ermann, M., et al. (2015). Targeting deubiquitinase activity with a novel small-molecule inhibitor as therapy for B-cell malignancies. Blood, 125(23), 3588–3597. https://doi.org/10.1182/blood-2014-10-605584.
6. Reyes-Turcu, F. E., Ventii, K. H., & Wilkinson, K. D. (2009). Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annual Review of Biochemistry, 78, 363–397. https://doi.org/10.1146/annurev.biochem.78.082307.091526.
7. Amerik, A. Y., & Hochstrasser, M. (2004). Mechanism and function of deubiquitinating enzymes. Biochimica et Biophysica Acta, 1695(1–3), 189–207. https://doi.org/10.1016/j.bbamcr.2004.10.003.
8. Balakirev, M. Y., Tcherniuk, S. O., Jaquinod, M., & Chroboczek, J. (2003). Otubains: a new family of cysteine proteases in the ubiquitin pathway. EMBO Reports, 4(5), 517–522. https://doi.org/10.1038/sj.embor.embor824.
9. Liu, C. W., & Jacobson, A. D. (2013). Functions of the 19S complex in proteasomal degradation. Trends in Biochemical Sciences, 38(2), 103–110. https://doi.org/10.1016/j.tibs.2012.11.009.
10. Lam, Y. A., Xu, W., DeMartino, G. N., & Cohen, R. E. (1997). Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome. Nature, 385(6618), 737–740. https://doi.org/10.1038/385737a0.
11. Hamazaki, J., Iemura, S., Natsume, T., Yashiroda, H., Tanaka, K., & Murata, S. (2006). A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes. The EMBO Journal, 25(19), 4524–4536. https://doi.org/10.1038/sj.emboj.7601338.
12. Yao, T., & Cohen, R. E. (2002). A cryptic protease couples deubiquitination and degradation by the proteasome. Nature, 419(6905), 403–407. https://doi.org/10.1038/nature01071.
13. Yao, T., Song, L., Xu, W., DeMartino, G. N., Florens, L., Swanson, S. K., et al. (2006). Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nature Cell Biology, 8(9), 994–1002. https://doi.org/10.1038/ncb1460.
14. Verma, R., Aravind, L., Oania, R., McDonald, W. H., Yates 3rd, J. R., Koonin, E. V., et al. (2002). Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science, 298(5593), 611–615. https://doi.org/10.1126/science.1075898.
15. Groll, M., Ditzel, L., Lowe, J., Stock, D., Bochtler, M., Bartunik, H. D., et al. (1997). Structure of 20S proteasome from yeast at 2.4 Å resolution. Nature, 386(6624), 463–471. https://doi.org/10.1038/386463a0.
16. Unno, M., Mizushima, T., Morimoto, Y., Tomisugi, Y., Tanaka, K., Yasuoka, N., et al. (2002). The structure of the mammalian 20S proteasome at 2.75 Å resolution. Structure, 10(5), 609–618.
17. Kisselev, A. F., Akopian, T. N., Castillo, V., & Goldberg, A. L. (1999). Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown. Molecular Cell, 4(3), 395–402.
18. Micel, L. N., Tentler, J. J., Smith, P. G., & Eckhardt, G. S. (2013). Role of ubiquitin ligases and the proteasome in oncogenesis: novel targets for anticancer therapies. Journal of Clinical Oncology, 31(9), 1231–1238. https://doi.org/10.1200/JCO.2012.44.0958.
19. D'Arcy, P., & Linder, S. (2014). Molecular pathways: translational potential of deubiquitinases as drug targets. Clinical Cancer Research, 20(15), 3908–3914. https://doi.org/10.1158/1078-0432.ccr-14-0568.
20. Laplante, M., & Sabatini, D. M. (2012). mTOR signaling in growth control and disease. Cell, 149(2), 274–293. https://doi.org/10.1016/j.cell.2012.03.017.
21. Hartl, F. U., & Hayer-Hartl, M. (2009). Converging concepts of protein folding in vitro and in vivo. Nature Structural & Molecular Biology, 16(6), 574–581. https://doi.org/10.1038/nsmb.1591.
22. Tu, B. P., & Weissman, J. S. (2004). Oxidative protein folding in eukaryotes: mechanisms and consequences. The Journal of Cell Biology, 164(3), 341–346. https://doi.org/10.1083/jcb.200311055.
23. Brnjic, S., Mazurkiewicz, M., Fryknas, M., Sun, C., Zhang, X., Larsson, R., et al. (2014). Induction of tumor cell apoptosis by a proteasome deubiquitinase inhibitor is associated with oxidative stress. Antioxidants & Redox Signaling, 21(17), 2271–2285. https://doi.org/10.1089/ars.2013.5322.
24. Fribley, A., & Wang, C. Y. (2006). Proteasome inhibitor induces apoptosis through induction of endoplasmic reticulum stress. Cancer Biology & Therapy, 5(7), 745–748.
25. Perez-Galan, P., Roue, G., Villamor, N., Montserrat, E., Campo, E., & Colomer, D. (2006). The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood, 107(1), 257–264. https://doi.org/10.1182/blood-2005-05-2091.
26. Ling, Y. H., Liebes, L., Zou, Y., & Perez-Soler, R. (2003). Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells. The Journal of Biological Chemistry, 278(36), 33714–33723. https://doi.org/10.1074/jbc.M302559200.
27. Yu, C., Rahmani, M., Dent, P., & Grant, S. (2004). The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor bortezomib. Experimental Cell Research, 295(2), 555–566. https://doi.org/10.1016/j.yexcr.2004.02.001.
28. Hideshima, T., Ikeda, H., Chauhan, D., Okawa, Y., Raje, N., Podar, K., et al. (2009). Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood, 114(5), 1046–1052. https://doi.org/10.1182/blood-2009-01-199604.
29. Bedford, L., Lowe, J., Dick, L. R., Mayer, R. J., & Brownell, J. E. (2011). Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nature Reviews. Drug Discovery, 10(1), 29–46. https://doi.org/10.1038/nrd3321.
30. Yew, P. R. (2001). Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators. Journal of Cellular Physiology, 187(1), 1–10. https://doi.org/10.1002/1097-4652(2001)9999:9999<1::AID-JCP1049>3.0.CO;2-O.
31. Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008). An oncogene-induced DNA damage model for cancer development. Science, 319(5868), 1352–1355. https://doi.org/10.1126/science.1140735.
32. Burgess, A., Chia, K. M., Haupt, S., Thomas, D., Haupt, Y., & Lim, E. (2016). Clinical overview of MDM2/X-targeted therapies. Frontiers in Oncology, 6, 7. https://doi.org/10.3389/fonc.2016.00007.
33. Saha, M. N., Qiu, L., & Chang, H. (2013). Targeting p53 by small molecules in hematological malignancies. Journal of Hematology & Oncology, 6, 23. https://doi.org/10.1186/1756-8722-6-23.
34. Citri, A., Alroy, I., Lavi, S., Rubin, C., Xu, W., Grammatikakis, N., et al. (2002). Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. The EMBO Journal, 21(10), 2407–2417. https://doi.org/10.1093/emboj/21.10.2407.
35. Howell, A. (2006). Pure oestrogen antagonists for the treatment of advanced breast cancer. Endocrine-Related Cancer, 13(3), 689–706. https://doi.org/10.1677/erc.1.00846.
36. Salami, J., & Crews, C. M. (2017). Waste disposal—an attractive strategy for cancer therapy. Science, 355(6330), 1163–1167. https://doi.org/10.1126/science.aam7340.
37. Kumar, S. K., Bensinger, W. I., Zimmerman, T. M., Reeder, C. B., Berenson, J. R., Berg, D., et al. (2014). Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood, 124(7), 1047–1055. https://doi.org/10.1182/blood-2014-01-548941.
38. Kontopodis, E., Kotsakis, A., Kentepozidis, N., Syrigos, K., Ziras, N., Moutsos, M., et al. (2016). A phase II, open-label trial of bortezomib (VELCADE((R))) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non-small cell lung cancer. Cancer Chemotherapy and Pharmacology, 77(5), 949–956. https://doi.org/10.1007/s00280-016-2997-7.
39. Zhao, Y., Foster, N. R., Meyers, J. P., Thomas, S. P., Northfelt, D. W., Rowland Jr., K. M., et al. (2015). A phase I/II study of bortezomib in combination with paclitaxel, carboplatin, and concurrent thoracic radiation therapy for non-small-cell lung cancer: North Central Cancer Treatment Group (NCCTG)-N0321. Journal of Thoracic Oncology, 10(1), 172–180. https://doi.org/10.1097/JTO.0000000000000383.
40. Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P., & Anderson, K. C. (2005). Proteasome inhibitor therapy in multiple myeloma. Molecular Cancer Therapeutics, 4(4), 686–692. https://doi.org/10.1158/1535-7163.MCT-04-0338.
41. Meister, S., Schubert, U., Neubert, K., Herrmann, K., Burger, R., Gramatzki, M., et al. (2007). Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition. Cancer Research, 67(4), 1783–1792. https://doi.org/10.1158/0008-5472.CAN-06-2258.
42. Campo, E., & Rule, S. (2015). Mantle cell lymphoma: evolving management strategies. Blood, 125(1), 48–55. https://doi.org/10.1182/blood-2014-05-521898.
43. Jares, P., Colomer, D., & Campo, E. (2012). Molecular pathogenesis of mantle cell lymphoma. The Journal of Clinical Investigation, 122(10), 3416–3423. https://doi.org/10.1172/JCI61272.
44. Kane, R. C., Bross, P. F., Farrell, A. T., & Pazdur, R. (2003). Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. The Oncologist, 8(6), 508–513.
45. Fisher, R. I., Bernstein, S. H., Kahl, B. S., Djulbegovic, B., Robertson, M. J., de Vos, S., et al. (2006). Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. Journal of Clinical Oncology, 24(30), 4867–4874. https://doi.org/10.1200/jco.2006.07.9665.
46. San Miguel, J. F., Schlag, R., Khuageva, N. K., Dimopoulos, M. A., Shpilberg, O., Kropff, M., et al. (2008). Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. The New England Journal of Medicine, 359(9), 906–917. https://doi.org/10.1056/NEJMoa0801479.
47. Adams, J. (2004). The development of proteasome inhibitors as anticancer drugs. Cancer Cell, 5(5), 417–421.
48. Sunwoo, J. B., Chen, Z., Dong, G., Yeh, N., Crowl Bancroft, C., Sausville, E., et al. (2001). Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clinical Cancer Research, 7(5), 1419–1428.
49. Hideshima, T., Richardson, P., Chauhan, D., Palombella, V. J., Elliott, P. J., Adams, J., et al. (2001). The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Research, 61(7), 3071–3076.
50. Pham, L. V., Tamayo, A. T., Yoshimura, L. C., Lo, P., & Ford, R. J. (2003). Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. Journal of Immunology, 171(1), 88–95.
51. Baiz, D., Pozzato, G., Dapas, B., Farra, R., Scaggiante, B., Grassi, M., et al. (2009). Bortezomib arrests the proliferation of hepatocellular carcinoma cells HepG2 and JHH6 by differentially affecting E2F1, p21 and p27 levels. Biochimie, 91(3), 373–382. https://doi.org/10.1016/j.biochi.2008.10.015.
52. Yang, Y., Ikezoe, T., Saito, T., Kobayashi, M., Koeffler, H. P., & Taguchi, H. (2004). Proteasome inhibitor PS-341 induces growth arrest and apoptosis of non-small cell lung cancer cells via the JNK/c-Jun/AP-1 signaling. Cancer Science, 95(2), 176–180.
53. Vaziri, S. A., Grabowski, D. R., Hill, J., Rybicki, L. R., Burk, R., Bukowski, R. M., et al. (2009). Inhibition of proteasome activity by bortezomib in renal cancer cells is p53 dependent and VHL independent. Anticancer Research, 29(8), 2961–2969.
54. Nikiforov, M. A., Riblett, M., Tang, W. H., Gratchouck, V., Zhuang, D., Fernandez, Y., et al. (2007). Tumor cell-selective regulation of NOXA by c-MYC in response to proteasome inhibition. Proceedings of the National Academy of Sciences of the United States of America, 104(49), 19488–19493. https://doi.org/10.1073/pnas.0708380104.
55. Murray, M. Y., Auger, M. J., & Bowles, K. M. (2014). Overcoming bortezomib resistance in multiple myeloma. Biochemical Society Transactions, 42(4), 804–808. https://doi.org/10.1042/BST20140126.
56. Cavaletti, G., & Jakubowiak, A. J. (2010). Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. Leukemia & Lymphoma, 51(7), 1178–1187. https://doi.org/10.3109/10428194.2010.483303.
57. Moreau, P., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., Grishunina, M., et al. (2011). Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. The Lancet Oncology, 12(5), 431–440. https://doi.org/10.1016/S1470-2045(11)70081-X.
58. Moreau, P., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., Rekhtman, G., et al. (2015). Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica, 100(5), e207–e210. https://doi.org/10.3324/haematol.2014.118182.
59. Arnulf, B., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., van de Velde, H., et al. (2012). Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica, 97(12), 1925–1928. https://doi.org/10.3324/haematol.2012.067793.
60. Wang, L., Wang, K. F., Chang, B. Y., Chen, X. Q., & Xia, Z. J. (2015). Once-weekly subcutaneous administration of bortezomib in patients with multiple myeloma. Asian Pacific Journal of Cancer Prevention, 16(5), 2093–2098.
61. Chen, D., Frezza, M., Schmitt, S., Kanwar, J., & Dou, Q. P. (2011). Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Current Cancer Drug Targets, 11(3), 239–253.
62. Jagannath, S., Durie, B. G., Wolf, J., Camacho, E., Irwin, D., Lutzky, J., et al. (2005). Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. British Journal of Haematology, 129(6), 776–783. https://doi.org/10.1111/j.1365-2141.2005.05540.x.
63. Orlowski, R. Z., Voorhees, P. M., Garcia, R. A., Hall, M. D., Kudrik, F. J., Allred, T., et al. (2005). Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. Blood, 105(8), 3058–3065. https://doi.org/10.1182/blood-2004-07-2911.
64. Hainsworth, J. D., Meluch, A. A., Spigel, D. R., Barton Jr., J., Simons, L., Meng, C., et al. (2007). Weekly docetaxel and bortezomib as first-line treatment for patients with hormone-refractory prostate cancer: a Minnie Pearl Cancer Research Network phase II trial. Clinical Genitourinary Cancer, 5(4), 278–283. https://doi.org/10.3816/CGC.2007.n.004.
65. Lu, S., Chen, Z., Yang, J., Chen, L., Gong, S., Zhou, H., et al. (2008). Overexpression of the PSMB5 gene contributes to bortezomib resistance in T-lymphoblastic lymphoma/leukemia cells derived from Jurkat line. Experimental Hematology, 36(10), 1278–1284. https://doi.org/10.1016/j.exphem.2008.04.013.
66. Lu, S., Yang, J., Chen, Z., Gong, S., Zhou, H., Xu, X., et al. (2009). Different mutants of PSMB5 confer varying bortezomib resistance in T lymphoblastic lymphoma/leukemia cells derived from the Jurkat cell line. Experimental Hematology, 37(7), 831–837. https://doi.org/10.1016/j.exphem.2009.04.001.
67. Oerlemans, R., Franke, N. E., Assaraf, Y. G., Cloos, J., van Zantwijk, I., Berkers, C. R., et al. (2008). Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood, 112(6), 2489–2499. https://doi.org/10.1182/blood-2007-08-104950.
68. Politou, M., Karadimitris, A., Terpos, E., Kotsianidis, I., Apperley, J. F., & Rahemtulla, A. (2006). No evidence of mutations of the PSMB5 (beta-5 subunit of proteasome) in a case of myeloma with clinical resistance to Bortezomib. Leukemia Research, 30(2), 240–241. https://doi.org/10.1016/j.leukres.2005.06.014.
69. Nawrocki, S. T., Carew, J. S., Pino, M. S., Highshaw, R. A., Andtbacka, R. H., Dunner Jr., K., et al. (2006). Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Research, 66(7), 3773–3781. https://doi.org/10.1158/0008-5472.CAN-05-2961.
70. Richardson, P. G., Schlossman, R. L., Alsina, M., Weber, D. M., Coutre, S. E., Gasparetto, C., et al. (2013). PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood, 122(14), 2331–2337. https://doi.org/10.1182/blood-2013-01-481325.
71. Smith, A. J., Dai, H., Correia, C., Takahashi, R., Lee, S. H., Schmitz, I., et al. (2011). Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells. The Journal of Biological Chemistry, 286(20), 17682–17692. https://doi.org/10.1074/jbc.M110.189092.
72. Hagenbuchner, J., Ausserlechner, M. J., Porto, V., David, R., Meister, B., Bodner, M., et al. (2010). The anti-apoptotic protein BCL2L1/Bcl-xL is neutralized by pro-apoptotic PMAIP1/Noxa in neuroblastoma, thereby determining bortezomib sensitivity independent of prosurvival MCL1 expression. The Journal of Biological Chemistry, 285(10), 6904–6912. https://doi.org/10.1074/jbc.M109.038331.
73. Premkumar, D. R., Jane, E. P., DiDomenico, J. D., Vukmer, N. A., Agostino, N. R., & Pollack, I. F. (2012). ABT-737 synergizes with bortezomib to induce apoptosis, mediated by Bid cleavage, Bax activation, and mitochondrial dysfunction in an Akt-dependent context in malignant human glioma cell lines. The Journal of Pharmacology and Experimental Therapeutics, 341(3), 859–872. https://doi.org/10.1124/jpet.112.191536.
74. Zhang, L., Littlejohn, J. E., Cui, Y., Cao, X., Peddaboina, C., & Smythe, W. R. (2010). Characterization of bortezomib-adapted I-45 mesothelioma cells. Molecular Cancer, 9, 110. https://doi.org/10.1186/1476-4598-9-110.
75. Herndon, T. M., Deisseroth, A., Kaminskas, E., Kane, R. C., Koti, K. M., Rothmann, M. D., et al. (2013). U.S. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma. Clinical Cancer Research, 19(17), 4559–4563. https://doi.org/10.1158/1078-0432.CCR-13-0755.
76. Kuhn, D. J., Chen, Q., Voorhees, P. M., Strader, J. S., Shenk, K. D., Sun, C. M., et al. (2007). Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood, 110(9), 3281–3290. https://doi.org/10.1182/blood-2007-01-065888.
77. Parlati, F., Lee, S. J., Aujay, M., Suzuki, E., Levitsky, K., Lorens, J. B., et al. (2009). Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. Blood, 114(16), 3439–3447. https://doi.org/10.1182/blood-2009-05-223677.
78. Demo, S. D., Kirk, C. J., Aujay, M. A., Buchholz, T. J., Dajee, M., Ho, M. N., et al. (2007). Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Research, 67(13), 6383–6391. https://doi.org/10.1158/0008-5472.CAN-06-4086.
79. Kisselev, A. F., & Goldberg, A. L. (2001). Proteasome inhibitors: from research tools to drug candidates. Chemistry & Biology, 8(8), 739–758.
80. Mitsiades, C. S., Hayden, P. J., Anderson, K. C., & Richardson, P. G. (2007). From the bench to the bedside: emerging new treatments in multiple myeloma. Best Practice & Research. Clinical Haematology, 20(4), 797–816. https://doi.org/10.1016/j.beha.2007.09.008.
81. Jakubowiak, A. J. (2014). Evolution of carfilzomib dose and schedule in patients with multiple myeloma: a historical overview. Cancer Treatment Reviews, 40(6), 781–790. https://doi.org/10.1016/j.ctrv.2014.02.005.
82. Berenson, J. R., Cartmell, A., Bessudo, A., Lyons, R. M., Harb, W., Tzachanis, D., et al. (2016). CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood, 127(26), 3360–3368. https://doi.org/10.1182/blood-2015-11-683854.
83. Lendvai, N., Hilden, P., Devlin, S., Landau, H., Hassoun, H., Lesokhin, A. M., et al. (2014). A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma. Blood, 124(6), 899–906. https://doi.org/10.1182/blood-2014-02-556308.
84. Siegel, D., Martin, T., Nooka, A., Harvey, R. D., Vij, R., Niesvizky, R., et al. (2013). Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica, 98(11), 1753–1761. https://doi.org/10.3324/haematol.2013.089334.
85. Zhou, H. J., Aujay, M. A., Bennett, M. K., Dajee, M., Demo, S. D., Fang, Y., et al. (2009). Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). Journal of Medicinal Chemistry, 52(9), 3028–3038. https://doi.org/10.1021/jm801329v.
86. Chauhan, D., Singh, A. V., Aujay, M., Kirk, C. J., Bandi, M., Ciccarelli, B., et al. (2010). A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood, 116(23), 4906–4915. https://doi.org/10.1182/blood-2010-04-276626.
87. Zang, Y., Thomas, S. M., Chan, E. T., Kirk, C. J., Freilino, M. L., DeLancey, H. M., et al. (2012). Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy. Clinical Cancer Research, 18(20), 5639–5649. https://doi.org/10.1158/1078-0432.CCR-12-1213.
88. Roccaro, A. M., Sacco, A., Aujay, M., Ngo, H. T., Azab, A. K., Azab, F., et al. (2010). Selective inhibition of chymotrypsin-like activity of the immunoproteasome and constitutive proteasome in Waldenstrom macroglobulinemia. Blood, 115(20), 4051–4060. https://doi.org/10.1182/blood-2009-09-243402.
89. Hurchla, M. A., Garcia-Gomez, A., Hornick, M. C., Ocio, E. M., Li, A., Blanco, J. F., et al. (2013). The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia, 27(2), 430–440. https://doi.org/10.1038/leu.2012.183.
90. Infante, J. R., Mendelson, D. S., Burris 3rd, H. A., Bendell, J. C., Tolcher, A. W., Gordon, M. S., et al. (2016). A first-in-human dose-escalation study of the oral proteasome inhibitor oprozomib in patients with advanced solid tumors. Investigational New Drugs, 34(2), 216–224. https://doi.org/10.1007/s10637-016-0327-x.
91. Muz, B., Ghazarian, R. N., Ou, M., Luderer, M. J., Kusdono, H. D., & Azab, A. K. (2016). Spotlight on ixazomib: potential in the treatment of multiple myeloma. Drug Design, Development and Therapy, 10, 217–226. https://doi.org/10.2147/DDDT.S93602.
92. Offidani, M., Corvatta, L., Caraffa, P., Gentili, S., Maracci, L., & Leoni, P. (2014). An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma. Onco Targets Ther, 7, 1793–1800. https://doi.org/10.2147/OTT.S49187.
93. Kupperman, E., Lee, E. C., Cao, Y., Bannerman, B., Fitzgerald, M., Berger, A., et al. (2010). Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Research, 70(5), 1970–1980. https://doi.org/10.1158/0008-5472.CAN-09-2766.
94. Lee, E. C., Fitzgerald, M., Bannerman, B., Donelan, J., Bano, K., Terkelsen, J., et al. (2011). Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clinical Cancer Research, 17(23), 7313–7323. https://doi.org/10.1158/1078-0432.CCR-11-0636.
95. Chauhan, D., Tian, Z., Zhou, B., Kuhn, D., Orlowski, R., Raje, N., et al. (2011). In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clinical Cancer Research, 17(16), 5311–5321. https://doi.org/10.1158/1078-0432.CCR-11-0476.
96. Tian, Z., Zhao, J. J., Tai, Y. T., Amin, S. B., Hu, Y., Berger, A. J., et al. (2012). Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood, 120(19), 3958–3967. https://doi.org/10.1182/blood-2012-01-401794.
97. Kumar, S. K., Berdeja, J. G., Niesvizky, R., Lonial, S., Laubach, J. P., Hamadani, M., et al. (2014). Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. The Lancet Oncology, 15(13), 1503–1512. https://doi.org/10.1016/S1470-2045(14)71125-8.
98. D'Arcy, P., Brnjic, S., Olofsson, M. H., Fryknas, M., Lindsten, K., De Cesare, M., et al. (2011). Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nature Medicine, 17(12), 1636–1640. https://doi.org/10.1038/nm.2536.
99. Wang, X., Stafford, W., Mazurkiewicz, M., Fryknas, M., Brjnic, S., Zhang, X., et al. (2014). The 19S deubiquitinase inhibitor b-AP15 is enriched in cells and elicits rapid commitment to cell death. Molecular Pharmacology, 85(6), 932–945. https://doi.org/10.1124/mol.113.091322.
100. Paulus, A., Chitta, K., Akhtar, S., Personett, D., Miller, K. C., Thompson, K. J., et al. (2014). AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenstrom macroglobulinaemia. British Journal of Haematology, 164(3), 352–365. https://doi.org/10.1111/bjh.12633.
101. Wang, X., Mazurkiewicz, M., Hillert, E. K., Olofsson, M. H., Pierrou, S., Hillertz, P., et al. (2016). The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. Scientific Reports, 6, 26979. https://doi.org/10.1038/srep26979.
102. Selvaraju, K., Mazurkiewicz, M., Wang, X., Gullbo, J., Linder, S., & D'Arcy, P. (2015). Inhibition of proteasome deubiquitinase activity: a strategy to overcome resistance to conventional proteasome inhibitors? Drug Resistance Updates, 21-22, 20–29. https://doi.org/10.1016/j.drup.2015.06.001.
103. Bartholomeusz, G. A., Talpaz, M., Kapuria, V., Kong, L. Y., Wang, S., Estrov, Z., et al. (2007). Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood, 109(8), 3470–3478. https://doi.org/10.1182/blood-2006-02-005579.
104. Bartholomeusz, G., Talpaz, M., Bornmann, W., Kong, L. Y., & Donato, N. J. (2007). Degrasyn activates proteasomal-dependent degradation of c-Myc. Cancer Research, 67(8), 3912–3918. https://doi.org/10.1158/0008-5472.CAN-06-4464.
105. Schwickart, M., Huang, X., Lill, J. R., Liu, J., Ferrando, R., French, D. M., et al. (2010). Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature, 463(7277), 103–107. https://doi.org/10.1038/nature08646.
106. Chauhan, D., Tian, Z., Nicholson, B., Kumar, K. G., Zhou, B., Carrasco, R., et al. (2012). A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell, 22(3), 345–358. https://doi.org/10.1016/j.ccr.2012.08.007.
107. Malapelle, U., Morra, F., Ilardi, G., Visconti, R., Merolla, F., Cerrato, A., et al. (2017). USP7 inhibitors, downregulating CCDC6, sensitize lung neuroendocrine cancer cells to PARP-inhibitor drugs. Lung Cancer, 107, 41–49. https://doi.org/10.1016/j.lungcan.2016.06.015.
108. Morra, F., Merolla, F., Napolitano, V., Ilardi, G., Miro, C., Paladino, S., et al. (2017). The combined effect of USP7 inhibitors and PARP inhibitors in hormone-sensitive and castration-resistant prostate cancer cells. Oncotarget, 8(19), 31815–31829. 10.18632/oncotarget.16463.
109. An, T., Gong, Y., Li, X., Kong, L., Ma, P., Gong, L., et al. (2017). USP7 inhibitor P5091 inhibits Wnt signaling and colorectal tumor growth. Biochemical Pharmacology, 131, 29–39. https://doi.org/10.1016/j.bcp.2017.02.011.
110. Carra, G., Panuzzo, C., Torti, D., Parvis, G., Crivellaro, S., Familiari, U., et al. (2017). Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: a strategy to overcome TP53 mutated/deleted clones. Oncotarget. 10.18632/oncotarget.16348.
111. Das, D. S., Ray, A., Das, A., Song, Y., Tian, Z., Oronsky, B., et al. (2016). A novel hypoxia-selective epigenetic agent RRx-001 triggers apoptosis and overcomes drug resistance in multiple myeloma cells. Leukemia, 30(11), 2187–2197. https://doi.org/10.1038/leu.2016.96.
112. Scicinski, J., Oronsky, B., Ning, S., Knox, S., Peehl, D., Kim, M. M., et al. (2015). NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001. Redox Biology, 6, 1–8. https://doi.org/10.1016/j.redox.2015.07.002.
113. Ning, S., Sekar, T. V., Scicinski, J., Oronsky, B., Peehl, D. M., Knox, S. J., et al. (2015). Nrf2 activity as a potential biomarker for the pan-epigenetic anticancer agent, RRx-001. Oncotarget, 6(25), 21547–21556. 10.18632/oncotarget.4249.
114. Byun, S., Lee, S. Y., Lee, J., Jeong, C. H., Farrand, L., Lim, S., et al. (2013). USP8 is a novel target for overcoming gefitinib resistance in lung cancer. Clinical Cancer Research, 19(14), 3894–3904. https://doi.org/10.1158/1078-0432.CCR-12-3696.
115. Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., et al. (2005). Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Medicine, 2(3), e73. https://doi.org/10.1371/journal.pmed.0020073.
116. Cichewicz, R. H., & Kouzi, S. A. (2004). Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Medicinal Research Reviews, 24(1), 90–114. https://doi.org/10.1002/med.10053.
117. Mullauer, F. B., Kessler, J. H., & Medema, J. P. (2010). Betulinic acid, a natural compound with potent anticancer effects. Anti-Cancer Drugs, 21(3), 215–227. https://doi.org/10.1097/CAD.0b013e3283357c62.
118. Reiner, T., Parrondo, R., de Las Pozas, A., Palenzuela, D., & Perez-Stable, C. (2013). Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity. PLoS One, 8(2), e56234. https://doi.org/10.1371/journal.pone.0056234.
119. Potze, L., Di Franco, S., Grandela, C., Pras-Raves, M. L., Picavet, D. I., van Veen, H. A., et al. (2016). Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification. Oncogene, 35(4), 427–437. https://doi.org/10.1038/onc.2015.102.
120. Currie, E., Schulze, A., Zechner, R., Walther, T. C., & Farese Jr., R. V. (2013). Cellular fatty acid metabolism and cancer. Cell Metabolism, 18(2), 153–161. https://doi.org/10.1016/j.cmet.2013.05.017.
121. Li, J., Yakushi, T., Parlati, F., Mackinnon, A. L., Perez, C., Ma, Y., et al. (2017). Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11. Nature Chemical Biology, 13(5), 486–493. https://doi.org/10.1038/nchembio.2326.
122. Cohen, S. M. (2017). A bioinorganic approach to fragment-based drug discovery targeting metalloenzymes. Accounts of Chemical Research. https://doi.org/10.1021/acs.accounts.7b00242.
123. Brownell, J. E., Sintchak, M. D., Gavin, J. M., Liao, H., Bruzzese, F. J., Bump, N. J., et al. (2010). Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Molecular Cell, 37(1), 102–111. https://doi.org/10.1016/j.molcel.2009.12.024.
124. Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., et al. (2009). An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature, 458(7239), 732–736. https://doi.org/10.1038/nature07884.
125. Shah, J. J., Jakubowiak, A. J., O'Connor, O. A., Orlowski, R. Z., Harvey, R. D., Smith, M. R., et al. (2016). Phase I study of the novel investigational NEDD8-activating enzyme inhibitor pevonedistat (MLN4924) in patients with relapsed/refractory multiple myeloma or lymphoma. Clinical Cancer Research, 22(1), 34–43. https://doi.org/10.1158/1078-0432.CCR-15-1237.
126. Bhatia, S., Pavlick, A. C., Boasberg, P., Thompson, J. A., Mulligan, G., Pickard, M. D., et al. (2016). A phase I study of the investigational NEDD8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924) in patients with metastatic melanoma. Investigational New Drugs, 34(4), 439–449. https://doi.org/10.1007/s10637-016-0348-5.
127. Sarantopoulos, J., Shapiro, G. I., Cohen, R. B., Clark, J. W., Kauh, J. S., Weiss, G. J., et al. (2016). Phase I study of the investigational NEDD8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924) in patients with advanced solid tumors. Clinical Cancer Research, 22(4), 847–857. https://doi.org/10.1158/1078-0432.CCR-15-1338.
128. Xu, G. W., Ali, M., Wood, T. E., Wong, D., Maclean, N., Wang, X., et al. (2010). The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood, 115(11), 2251–2259. https://doi.org/10.1182/blood-2009-07-231191.
129. Yang, Y., Kitagaki, J., Dai, R. M., Tsai, Y. C., Lorick, K. L., Ludwig, R. L., et al. (2007). Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Research, 67(19), 9472–9481. https://doi.org/10.1158/0008-5472.CAN-07-0568.
130. Ungermannova, D., Parker, S. J., Nasveschuk, C. G., Chapnick, D. A., Phillips, A. J., Kuchta, R. D., et al. (2012). Identification and mechanistic studies of a novel ubiquitin E1 inhibitor. Journal of Biomolecular Screening, 17(4), 421–434. https://doi.org/10.1177/1087057111433843.
131. Asuthkar, S., Velpula, K. K., Elustondo, P. A., Demirkhanyan, L., & Zakharian, E. (2015). TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells. Oncotarget, 6(19), 17221–17236. 10.18632/oncotarget.3948.
132. Grace, C. R., Ban, D., Min, J., Mayasundari, A., Min, L., Finch, K. E., et al. (2016). Monitoring ligand-induced protein ordering in drug discovery. Journal of Molecular Biology, 428(6), 1290–1303. https://doi.org/10.1016/j.jmb.2016.01.016.
133. Zheng, T., Wang, J., Song, X., Meng, X., Pan, S., Jiang, H., et al. (2010). Nutlin-3 cooperates with doxorubicin to induce apoptosis of human hepatocellular carcinoma cells through p53 or p73 signaling pathways. Journal of Cancer Research and Clinical Oncology, 136(10), 1597–1604. https://doi.org/10.1007/s00432-010-0817-8.
134. Roh, J. L., Kang, S. K., Minn, I., Califano, J. A., Sidransky, D., & Koch, W. M. (2011). p53-reactivating small molecules induce apoptosis and enhance chemotherapeutic cytotoxicity in head and neck squamous cell carcinoma. Oral Oncology, 47(1), 8–15. https://doi.org/10.1016/j.oraloncology.2010.10.011.
135. Endo, S., Yamato, K., Hirai, S., Moriwaki, T., Fukuda, K., Suzuki, H., et al. (2011). Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells. Cancer Science, 102(3), 605–613. https://doi.org/10.1111/j.1349-7006.2010.01821.x.
136. Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., et al. (2004). In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303(5659), 844–848. https://doi.org/10.1126/science.1092472.
137. Khoo, K. H., Verma, C. S., & Lane, D. P. (2014). Drugging the p53 pathway: understanding the route to clinical efficacy. Nature Reviews. Drug Discovery, 13(3), 217–236. https://doi.org/10.1038/nrd4236.
138. Lee, Y. M., Lim, J. H., Chun, Y. S., Moon, H. E., Lee, M. K., Huang, L. E., et al. (2009). Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha. Carcinogenesis, 30(10), 1768–1775. https://doi.org/10.1093/carcin/bgp196.