Targeting oncogenic Myc as a strategy for cancer treatment

Signal Transduction and Targeted Therapy

Volumn 3, Issue 1, 2018, Pages

  Chen, Hui ^a,b   Liu, Hudan ^a,b   Qing, Guoliang ^a,b  

^a ZHONGNAN HOSPITAL OF WUHAN UNIVERSITY   (China)

^b WUHAN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85050763688     PISSN: 20959907     EISSN: 20593635     Source Type: Journal    
DOI: 10.1038/s41392-018-0008-7     Document Type: Review

References (97)

1. Adhikary, S. & Eilers, M. Transcriptional regulation and transformation by Myc proteins. Nat. Rev. Mol. Cell Biol. 6, 635–645 (2005).
2. Pelengaris, S., Khan, M. & Evan, G. c-MYC: more than just a matter of life and death. Nat. Rev. Cancer 2, 764–776 (2002).
3. Dang, C. V. MYC on the path to cancer. Cell 149, 22–35 (2012).
4. Dang, C. V. et al. The c-Myc target gene network. Semin. Cancer Biol. 16, 253–264 (2006).
5. Meyer, N. & Penn, L. Z. Reflecting on 25 years with MYC. Nat. Rev. Cancer 8, 976–990 (2008).
6. Nie, Z. et al. c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell 151, 68–79 (2012).
7. Lin, C. Y. et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151, 56–67 (2012).
8. Shachaf, C. M. & Felsher, D. W. Tumor dormancy and MYC inactivation: pushing cancer to the brink of normalcy. Cancer Res. 65, 4471–4474 (2005).
9. Soucek, L. et al. Modelling Myc inhibition as a cancer therapy. Nature 455, 679–683 (2008).
10. Arvanitis, C. & Felsher, D. W. Conditional transgenic models define how MYC initiates and maintains tumorigenesis. Semin. Cancer Biol. 16, 313–317 (2006).
11. Delmore, J. E. et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146, 904–917 (2011).
12. Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010).
13. Tavana, O. et al. HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma. Nat. Med. 22, 1180–1186 (2016).
14. Otto, T. et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 15, 67–78 (2009).
15. Berg, T. et al. Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts. Proc. Natl Acad. Sci. USA 99, 3830–3835 (2002).
16. Haynes, S. R. et al. The bromodomain: a conserved sequence found in human, Drosophila and yeast proteins. Nucleic Acids Res. 20, 2603 (1992).
17. Yang, Z. et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol. Cell 19, 535–545 (2005).
18. Peterlin, B. M. & Price, D. H. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell 23, 297–305 (2006).
19. Dawson, M. A. et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478, 529–533 (2011).
20. Zuber, J. et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478, 524–528 (2011).
21. Mertz, J. A. et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc. Natl Acad. Sci. USA 108, 16669–16674 (2011).
22. Mazur, P. K. et al. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nat. Med. 21, 1163–1171 (2015).
23. Puissant, A. et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 3, 308–323 (2013).
24. Fisher, R. P. Secrets of a double agent: CDK7 in cell-cycle control and transcription. J. Cell. Sci. 118, 5171–5180 (2005).
25. Shiekhattar, R. et al. CDK-activating kinase complex is a component of human transcription factor TFIIH. Nature 374, 283–287 (1995).
26. Peng, J., Marshall, N. F. & Price, D. H. Identification of a cyclin subunit required for the function of Drosophila P-TEFb. J. Biol. Chem. 273, 13855–13860 (1998).
27. Heidemann, M., Hintermair, C., Voß, K. & Eick, D. Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription. Biochim. Biophys. Acta 1829, 55–62 (2013).
28. Chen, R., Keating, M. J., Gandhi, V. & Plunkett, W. Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood 106, 2513–2519 (2005).
29. Rahl, P. B. et al. c-Myc regulates transcriptional pause release. Cell 141, 432–445 (2010).
30. Chipumuro, E. et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell 159, 1126–1139 (2014).
31. Chapuy, B. et al. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell 24, 777–790 (2013).
32. Kwiatkowski, N. et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature 511, 616–620 (2014).
33. Garcia-Cuellar, M. P. et al. Efficacy of cyclin-dependent-kinase 9 inhibitors in a murine model of mixed-lineage leukemia. Leukemia 28, 1427–1435 (2014).
34. Bjornsti, M. A. & Houghton, P. J. The TOR pathway: a target for cancer therapy. Nat. Rev. Cancer 4, 335–348 (2004).
35. Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006).
36. Kim, D. H. et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163–175 (2002).
37. Frost, P. et al. In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model. Blood 104, 4181–4187 (2004).
38. Chapuis, N. et al. Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia. Clin. Cancer Res. 16, 5424–5435 (2010).
39. Yu, K. et al. mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr. Relat. Cancer 8, 249–258 (2001).
40. Fernández-Miranda, G. & Méndez, R. The CPEB-family of proteins, translational control in senescence and cancer. Ageing Res. Rev. 11, 460–472 (2012).
41. Groisman, I. et al. Control of cellular senescence by CPEB. Genes Dev. 20, 2701–2712 (2006).
42. Ogami, K., Hosoda, N., Funakoshi, Y. & Hoshino, S. Antiproliferative protein Tob directly regulates c-myc proto-oncogene expression through cytoplasmic polyadenylation element-binding protein CPEB. Oncogene 33, 55–64 (2014).
43. Yada, M. et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 23, 2116–2125 (2004).
44. Welcker, M. et al. A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size. Curr. Biol. 14, 1852–1857 (2004).
45. Popov, N. et al. The ubiquitin-specific protease USP28 is required for MYC stability. Nat. Cell Biol. 9, 765–774 (2007).
46. Sun, X. X. et al. The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc. Proc. Natl Acad. Sci. USA 112, 3734–3739 (2015).
47. Bischoff, J. R. & Plowman, G. D. The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis. Trends Cell Biol. 9, 454–459 (1999).
48. Sasai, K., Treekitkarnmongkol, W., Kai, K., Katayama, H. & Sen, S. Functional significance of Aurora kinases-p53 protein family interactions in cancer. Front Oncol. 6, 247 (2016).
49. Takahashi, Y. et al. The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC. Ann. Oncol. 26, 935–942 (2015).
50. Yang, S. et al. Suppression of Aurora-A oncogenic potential by c-Myc downregulation. Exp. Mol. Med. 42, 759–767 (2010).
51. Brockmann, M. et al. Small molecule inhibitors of Aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell 24, 75–89 (2013).
52. Dauch, D. et al. A MYC-Aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer. Nat. Med. 22, 744–753 (2016).
53. Golsteyn, R. M., Lane, H. A., Mundt, K. E., Arnaud, L. & Nigg, E. A. The family of polo-like kinases. Prog. Cell Cycle Res. 2, 107–114 (1996).
54. Xiao, D. et al. Polo-like kinase-1 regulates Myc stabilization and activates a feedforward circuit promoting tumor cell survival. Mol. Cell 64, 493–506 (2016).
55. Nair, S. K. & Burley, S. K. X-ray structures of Myc–Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell 112, 193–205 (2003).
56. Wang, H. et al. Improved low molecular weight Myc–Max inhibitors. Mol. Cancer Ther. 6, 2399–2408 (2007).
57. Soucek, L. et al. Design and properties of a Myc derivative that efficiently homodimerizes. Oncogene 17, 2463–2472 (1998).
58. Soucek, L., Nasi, S. & Evan, G. I. Omomyc expression in skin prevents Myc-induced papillomatosis. Cell Death Differ. 11, 1038–1045 (2004).
59. Annibali, D. et al. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nat. Commun. 5, 4632 (2014).
60. Kaelin, W. G. Jr. The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer 5, 689–698 (2005).
61. Malumbres, M. & Barbacid, M. Cell cycle, cdks and cancer: a changing paradigm. Nat. Rev. Cancer 9, 153–166 (2009).
62. Kang, J., Sergio, C. M., Sutherland, R. L. & Musgrove, E. A. Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer cells. BMC Cancer 14, 32 (2014).
63. Goga, A., Yang, D., Tward, A. D., Morgan, D. O. & Bishop, J. M. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat. Med. 13, 820–827 (2007).
64. Peeper, D. S. et al. Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro. Oncogene 10, 39–48 (1995).
65. Göllner, S. et al. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia. Nat. Med. 23, 69–78 (2017).
66. Zhao, H. & Piwnica-Worms, H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell Biol. 21, 4129–4139 (2001).
67. Furnari, B., Rhind, N. & Russell, P. Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science 277, 1495–1497 (1997).
68. Höglund, A. et al. Therapeutic implications for the induced levels of Chk1 in Myc-expressing cancer cells. Clin. Cancer Res. 17, 7067–7079 (2011).
69. Dominguez-Sola, D. et al. Non-transcriptional control of DNA replication by c-Myc. Nature 448, 445–451 (2007).
70. Cole, K. A. et al. RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma. Proc. Natl Acad. Sci. USA 108, 3336–3341 (2011).
71. Murga, M. et al. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors. Nat. Struct. Mol. Biol. 18, 1331–1335 (2011).
72. Ferrao, P. T., Bukczynska, E. P., Johnstone, R. W. & McArthur, G. A. Efficacy of CHK inhibitors as single agents in MYC-driven lymphoma cells. Oncogene 31, 1661–1672 (2012).
73. DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G. & Thompson, C. B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7, 11–20 (2008).
74. Dang, C. V. A time for MYC: metabolism and therapy. Cold Spring Harb. Symp. Quant. Biol. 81, 79–83 (2016).
75. Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R. & Lazebnik, Y. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J. Cell Biol. 178, 93–105 (2007).
76. Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762–765 (2009).
77. Mullen, A. R. et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 481, 385–388 (2011).
78. Metallo, C. M. et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481, 380–384 (2011).
79. Qing, G. et al. ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22, 631–644 (2012).
80. Xiao, D. et al. Myc promotes glutaminolysis in human neuroblastoma through direct activation of glutaminase 2. Oncotarget 6, 40655–40666 (2015).
81. Jacque, N. et al. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood 126, 1346–1356 (2015).
82. Superti-Furga, G. et al. Where is the future of drug discovery for cancer? Cell 168, 564–565 (2017).
83. Fong, C. Y. et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature 525, 538–542 (2015).
84. Matkar, S. et al. An epigenetic pathway regulates sensitivity of breast cancer cells to HER2 inhibition via FOXO/c-Myc axis. Cancer Cell 28, 472–485 (2015).
85. Cicenas, J. et al. Roscovitine in cancer and other diseases. Ann. Transl. Med 3, 135 (2015).
86. Awan, F. T. et al. A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy. Ann. Hematol. 95, 1137–1143 (2016).
87. Vignot, S., Faivre, S., Aguirre, D. & Raymond, E. mTOR-targeted therapy of cancer with rapamycin derivatives. Ann. Oncol. 16, 525–537 (2005).
88. Xu, C. X. et al. The combination of RAD001 and NVP-BEZ235 exerts synergistic anticancer activity against non-small cell lung cancer in vitro and in vivo. PLoS ONE 6, e20899 (2011).
89. Pal, S. K., Reckamp, K., Yu, H. & Figlin, R. A. Akt inhibitors in clinical development for the treatment of cancer. Expert Opin. Investig. Drugs 19, 1355–1366 (2010).
90. Blackburn, J. S. et al. Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation. Cancer Cell 25, 366–378 (2014).
91. Gjertsen, B. T. & Schoffski, P. Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy. Leukemia 29, 11–19 (2015).
92. Schoffski, P. et al. A phase I, dose-escalation study of the novel Polo-like kinase inhibitor volasertib (BI 6727) in patients with advanced solid tumours. Eur. J. Cancer 48, 179–186 (2012).
93. Sebastian, M. et al. The efficacy and safety of BI 2536, a novel Plk-1 inhibitor, in patients with stage IIIB/IV non-small cell lung cancer who had relapsed after, or failed, chemotherapy: results from an open-label, randomized phase II clinical trial. J. Thorac. Oncol. 5, 1060–1067 (2010).
94. Awad, M. M. et al. An open-label, phase II study of the polo-like kinase-1 (Plk-1) inhibitor, BI 2536, in patients with relapsed small cell lung cancer (SCLC). Lung Cancer 104, 126–130 (2017).
95. Cassaday, R. D. et al. A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma. Clin. Lymphoma Myeloma Leuk. 15, 392–397 (2015).
96. Sen, T. et al. CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib. Cancer Res. 77, 3870–3884 (2017).
97. Hong, D. et al. Phase I study of LY2606368, a checkpoint kinase 1 inhibitor, in patients with advanced cancer. J. Clin. Oncol. 34, 1764–1771 (2016).