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Novel PBD inhibit NF-κB in hematologic cancers
manuscript; DBC performed experiments, analyzed data and revised the manuscript; KMR and DET conceived and super- vised the synthetic chemistry and revised the manuscript; PJG, KA, AGSP and EJW analyzed data and revised the manuscript; CDF provided vital reagents and revised the manuscript; CP conceived and supervised the cell biology experiments, analyzed data and revised the manuscript.
Acknowledgments
This work was supported by a grant (n. 12-1263/JGATCBR) from Worldwide Cancer Research (formerly AICR) to DET, KMR and CP in 2012. This support included a PhD stu- dentship held by DBC, which enabled all of the novel medicinal chemistry. CP, CDF and AGSP are also supported by a Bloodwise Programme Continuity Grant (18005).
References
1. Zheng C, Yin Q, Wu H. Structural studies of NF-κB signaling. Cell Res. 2011;21(1):183- 195.
2. Gasparini C, Celeghini C, Monasta L, Zauli G. NF-κB pathways in hematological malig- nancies. Cell Mol Life Sci. 2014;71(11):2083- 2102.
3. Hoffmann A, Natoli G, Ghosh G. Transcriptional regulation via the NF- kappaB signaling module. Oncogene. 2006;25(51):6706-6716.
4. Braun T, Carvalho G, Fabre C, Grosjean J, Fenaux P, Kroemer G. Targeting NF-kappaB in hematologic malignancies. Cell Death Differ. 2006;13(5):748-758.
5. Abdi J, Chen G, Chang H. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget. 2013;4(12):2186-2207.
6. Hewamana S, Alghazal S, Lin TT, et al. The NF-kappaB subunit Rel A is associated with in vitro survival and clinical disease progres- sion in chronic lymphocytic leukemia and represents a promising therapeutic target. Blood. 2008;111(9):4681-4689.
7. Merchionne F, Perosa F, Dammacco F. New therapies in multiple myeloma. Clin Exp Med. 2007;7(3):83-97.
8.Byrd JC,Brown JR,O’Brien S,etal.RES- ONATE Investigators. Ibrutinib versus ofa- tumumab in previously treated chronic lym- phoid leukemia. N Engl J Med. 2014;371(3):213-223.
9.Hideshima T, Ikeda H, Chauhan D, et al. Bortezomib induces canonical nuclear fac- tor-kappaB activation in multiple myeloma cells. Blood. 2009;114(5):1046-1052.
10.Ahn IE, Underbayev C, Albitar A, et al. Clonal evolution leading to ibrutinib resist- ance in chronic lymphocytic leukemia. Blood. 2017;129(11):1469-1479.
11.Wang CY, Mayo MW, Baldwin AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274(5288):784-787.
12. Hideshima T, Chauhan D, Richardson P, et al. NF-kappa B as a therapeutic target in mul- tiple myeloma. J Biol Chem. 2002;277(19): 16639-16647.
13. Pepper C, Hewamana S, Brennan P, Fegan C. NF-kappaB as a prognostic marker and ther- apeutic target in chronic lymphocytic leukemia. Future Oncol. 2009;5(7):1027- 1037.
14.Antonow D, Thurston DE. Synthesis of DNA-interactive pyrrolo[2,1-c [1,4]benzodi- azepines (PBDs). Chem Rev. 2011;111(4): 2815-2864.
15.Gerratana B. Biosynthesis, synthesis, and biological activities of pyrrolobenzodi- azepines. Med Res Rev. 2012;32(2):254-293.
16. Rahman KM, Vassoler H, James CH, Thurston DE. DNA sequence preference and adduct orientation of pyrrolo[2,1- c][1,4]benzodiazepine antitumor agents. ACS Med Chem Lett. 2010;1(8):427-432.
17. Puzanov I, Lee W, Chen AP, et al. Phase I pharmacokinetic and pharmacodynamic study of SJG-136, a novel DNA sequence selective minor groove cross-linking agent, in advanced solid tumors. Clin Cancer Res. 2011;17(11):3794-3802.
18. Mantaj J, Jackson PJ, Rahman KM, Thurston DE. From anthramycin to pyrrolobenzodi- azepine (PBD)-containing antibody-drug conjugates (ADCs). Angew Chem Int Ed Engl. 2017;56(2):462-488.
19. Kotecha M, Kluza J, Wells G, et al. Inhibition of DNA binding of the NF-Y transcription factor by the pyrrolobenzodiazepine- polyamide conjugate GWL-78. Mol Cancer Ther. 2008;7(5):1319-1328.
20. Hu WP, Tsai FY, Yu HS, Sung PJ, Chang LS, Wang JJ. Induction of apoptosis by DC-81- indole conjugate agent through NF-kappaB and JNK/AP-1 pathway. Chem Res Toxicol. 2008;21(7):1330-1336.
21. Rahman KM, Jackson PJ, James CH, et al. GC-targeted C8-linked pyrrolobenzodi- azepine-biaryl conjugates with femtomolar in vitro cytotoxicity and in vivo antitumor activity in mouse models. J Med Chem. 2013;56(7):2911-2935.
22. Chou TC. Drug combination studies and their synergy quantification using the Chou- Talalay method. Cancer Res. 2010;70(2): 440-446.
23. Demchenko YN, Glebov OK, Zingone A, Keats JJ, Bergsagel PL, Kuehl WM. Classical and/or alternative NF-kappaB pathway acti- vation in multiple myeloma. Blood. 2010;115(17):3541-3552.
24.Keats JJ, Fonseca R, Chesi M, et al. Promiscuous mutations activate the non- canonical NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007;12(2):131-144.
25. Zhang B, Kirov S, Snoddy J.WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 2005;33(Web Server issue):W741-48.
26. Hertlein E, Byrd JC. Signalling to drug resist- ance in CLL. Best Pract Res Clin Haematol. 2010;23(1):121-131.
27. Markovina S, Callander NS, O'Connor SL, et al. Bortezomib-resistant nuclear factor- kappaB activity in multiple myeloma cells. Mol Cancer Res. 2008;6(8):1356-1364.
28. Diop F, Moia R, Favini C, et al. Biological and clinical implications of BIRC3 mutations in chronic lymphocytic leukemia. Haematologica. 2020;105(2):448-456.
29.Benedetti D, Tissino E, Pozzo F, et al. NOTCH1 mutations are associated with high CD49d expression in chronic lympho- cytic leukemia: link between the NOTCH1
and the NF-κB pathways. Leukemia.
2018;32(3):654-662.
30. Asslaber D, Wacht N, Leisch M, Qi Y, et al.
BIRC3 expression predicts CLL progression and defines treatment sensitivity via enhanced NF-κB nuclear translocation. Clin Cancer Res. 2019;25(6):1901-1912
31. Del Poeta G, Dal Bo M, Del Principe MI, et al. Clinical significance of c.7544-7545 del CT NOTCH1 mutation in chronic lympho- cytic leukaemia. Br J Haematol. 2013; 160(3):415-418.
32. Rossi D, Rasi S, Fabbri G, et al. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood. 2012;119(2):521.
33. Hoffmann A, Levchenko A, Scott ML, Baltimore D. The IkappaB-NF-kappaB sig- naling module: temporal control and selec- tive gene activation. Science. 2002;298 (5596):1241-1245.
34. Natoli G, Chiocca S. Nuclear ubiquitin ligas- es, NF-kappaB degradation, and the control of inflammation. Sci Signal. 2008;1(1):pe1.
35. Godwin P, Baird AM, Heavey S, Barr MP, O'Byrne KJ, Gately K. Targeting nuclear fac- tor-kappa B to overcome resistance to chemotherapy. Front Oncol. 2013;3:120.
36. Baumann P, Mandl-Weber S, Oduncu F, Schmidmaier R. Alkylating agents induce activation of NFkappaB in multiple myelo- ma cells. Leuk Res. 2008;32(7):1144-1147.
37. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906-917.
38. Murray MY, Auger MJ, Bowles KM. Overcoming bortezomib resistance in 548 multiple myeloma. Biochem Soc Trans. 2014;42(4):804-808.
39.Woyach JA, Bojnik E, Ruppert AS, et al. Bruton's tyrosine kinase (BTK) function is important to the development and expan- sion of chronic lymphocytic leukemia (CLL). Blood. 2014;123(8):1207-1213.
40.Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.
41. Herman SE, Mustafa RZ, Gyamfi JA, et al. Ibrutinib inhibits BCR and NF-κB signaling and reduces tumor proliferation in tissue- resident cells of patients with CLL. Blood. 2014;123(21):3286-3295.
42. Jayappa KD, Portell CA, Gordon VL, et al. Microenvironmental agonists generate de novo phenotypic resistance to combined ibrutinib plus venetoclax in CLL and MCL. Blood Adv. 2017;1(14):933-946.
43. Fabre C, Mimura N, Bobb K, et al. Dual inhi- bition of canonical and noncanonical NF-κB pathways demonstrates significant antitu- mor activities in multiple myeloma. Clin Cancer Res. 2012;18(17):4669-4681.
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