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CUDC-907 combined with venetoclax in AML
participated in the data analysis and interpretation; KH, GM, HE, TK and YG helped to draft the manuscript. All authors read and approved the final manuscript.
Funding
This study was supported by Jilin University, Changchun, China, the Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, and by grants from Projects of Jilin Province Science and Technology Development Plan (20180101277JC), the National Natural Science Foundation of China (NSFC 31671438 and NSFC 31471295), National Key Research and Development Program
of China (2017YFC1702103), Graduate Innovation Fund of Jilin University, Hyundai Hope on Wheels, LaFontaine Family/U Can-Cer Vive Foundation, Kids Without Cancer, Children’s Hospital of Michigan Foundation, Decerchio/Guisewite Family, Justin’s Gift, Elana Fund, Ginopolis/Karmanos Endowment and the Ring Screw Textron Endowed Chair for Pediatric Cancer Research. The Animal Model and Therapeutics Evaluation Core and Genomics Core are supported, in part, by NIH Center Grant P30 CA022453 to the Karmanos Cancer Institute at Wayne State University. The funders had no role in study design, data collection, analysis and interpretation of data, decision to publish, or preparation of the manuscript.
References
1. Niu X, Zhao J, Ma J, et al. Binding of released Bim to Mcl-1 is a mechanism of intrinsic resistance to ABT-199 which can be over- come by combination with daunorubicin or cytarabine in AML cells. Clin Cancer Res. 2016;22(17):4440-4451.
2. Knight T, Edwards H, Taub JW, Ge Y. Evaluating venetoclax and its potential in treatment-naive acute myeloid leukemia. Cancer Manag Res. 2019;11:3197-3213.
3. Luedtke DA, Niu X, Pan Y, et al. Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells. Signal Transduct Target Ther. 2017;2:17012.
4. Xie C, Edwards H, Caldwell JT, Wang G, Taub JW, Ge Y. Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage. Mol Oncol. 2015;9(2):409-421.
5. Knight T, Luedtke D, Edwards H, Taub JW, Ge Y. A delicate balance - the BCL-2 family and its role in apoptosis, oncogenesis, and cancer therapeutics. Biochem Pharmacol. 2019;162:250-261.
6. Zhao J, Niu X, Li X, et al. Inhibition of CHK1 enhances cell death induced by the Bcl-2- selective inhibitor ABT-199 in acute myeloid leukemia cells. Oncotarget. 2016; 7(23):34785-34799.
7. Kotian S, Zhang L, Boufraqech M, et al. Dual Inhibition of HDAC and tyrosine kinase aig- naling pathways with CUDC-907 inhibits thyroid cancer growth and metastases. Clin Cancer Res. 2017; 23(17):5044-5054.
8. Qian C, Lai CJ, Bao R, et al. Cancer network disruption by a single molecule inhibitor tar- geting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin Cancer Res. 2012;18(15):4104-4113.
9. Sun K, Atoyan R, Borek MA, et al. Dual HDAC and PI3K inhibitor CUDC-907 downregulates MYC and suppresses growth of MYC-dependent cancers. Mol Cancer Ther. 2017;16(2):285-299.
10. Younes A, Berdeja JG, Patel MR, et al. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose- escalation, phase 1 trial. Lancet Oncol. 2016;
17(5):622-631.
11. Li X, Su Y, Madlambayan G, et al.
Antileukemic activity and mechanism of action of the novel PI3K and histone deacetylase dual inhibitor CUDC-907 in acute myeloid leukemia. Haematologica. 2019;104(11):2225-2240.
12. Chen S, Dai Y, Pei XY, Grant S. Bim upregu- lation by histone deacetylase inhibitors mediates interactions with the Bcl-2 antago- nist ABT-737: evidence for distinct roles for Bcl-2, Bcl-xL, and Mcl-1. Mol Cell Biol. 2009; 29(23):6149-6169.
13. Fiskus W, Sharma S, Saha S, et al. Pre-clinical efficacy of combined therapy with novel beta-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells. Leukemia. 2015;29(6):1267-1278.
14. Qi W, Zhang W, Edwards H, et al. Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo. Cancer Biol Ther. 2015;16(12):1784-1793.
15. Aye Y, Li M, Long MJ, Weiss RS. Ribonucleotide reductase and cancer: bio- logical mechanisms and targeted therapies. Oncogene. 2015;34(16):2011-2021.
16. Rahmani M, Aust MM, Benson EC, Wallace L, Friedberg J, Grant S. PI3K/mTOR inhibi- tion markedly potentiates HDAC inhibitor activity in NHL cells through BIM- and MCL- 1-dependent mechanisms in vitro and in vivo. Clin Cancer Res. 2014;20(18):4849-4860.
17. Salvatori B, Iosue I, Djodji Damas N, et al. Critical role of c-Myc in acute myeloid leukemia involving direct regulation of miR- 26a and histone methyltransferase EZH2. Genes Cancer. 2011;2(5):585-592.
18. Ohanian M, Rozovski U, Kanagal- Shamanna R, et al. MYC protein expression is an important prognostic factor in acute myeloid leukemia. Leuk Lymphoma. 2019; 60(1):37-48.
19. Niu X, Wang G, Wang Y, et al. Acute myeloid leukemia cells harboring MLL fusion genes or with the acute promyelocyt- ic leukemia phenotype are sensitive to the Bcl-2-selective inhibitor ABT-199. Leukemia. 2014;28(7):1557-1560.
20. Ma J, Li X, Su Y, et al. Mechanisms respon- sible for the synergistic antileukemic interac- tions between ATR inhibition and cytara- bine in acute myeloid leukemia cells. Sci Rep. 2017;7:41950.
21. Xie C, Edwards H, Xu X, et al. Mechanisms
of synergistic antileukemic interactions between valproic acid and cytarabine in pediatric acute myeloid leukemia. Clin Cancer Res. 2010;16(22):5499-5510.
22. Edwards H, Xie C, LaFiura KM, et al. RUNX1 regulates phosphoinositide 3- kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia. Blood. 2009;114(13):2744-2752.
23. Su Y, Li X, Ma J, et al. Targeting PI3K, mTOR, ERK, and Bcl-2 signaling network shows superior antileukemic activity against AML ex vivo. Biochem Pharmacol. 2018; 148:13-26.
24. Luedtke DA, Su Y, Liu S, et al. Inhibition of XPO1 enhances cell death induced by ABT- 199 in acute myeloid leukaemia via Mcl-1. J Cell Mol Med. 2018;22(12):6099-6111.
25. Domina AM, Vrana JA, Gregory MA, Hann SR, Craig RW. MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol. Oncogene. 2004;23(31):5301-5315.
26. Hoffman B, Amanullah A, Shafarenko M, Liebermann DA. The proto-oncogene c-myc in hematopoietic development and leuke- mogenesis. Oncogene. 2002;21(21):3414- 3421.
27. Renneville A, Roumier C, Biggio V, et al. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia. 2008;22(5):915-931.
28. Pham LV, Huang S, Zhang H, et al. Strategic therapeutic targeting to overcome veneto- clax resistance in aggressive B-cell lym- phomas. Clin Cancer Res. 2018; 24(16): 3967-3980.
29. Gabay M, Li Y, Felsher DW. MYC activation is a hallmark of cancer initiation and mainte- nance. Cold Spring Harb Perspect Med. 2014;4(6).
30. Manning BD, Toker A. AKT/PKB signaling: navigating the network. Cell. 2017;169 (3):381-405.
31. Cinar M, Rosenfelt F, Rokhsar S, et al. Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for double hit and triple hit B-cell lymphomas. Leuk Res. 2015;39(7):730-738.
32. Eek D, Krohe M, Mazar I, et al. Patient- reported preferences for oral versus intra- venous administration for the treatment of cancer: a review of the literature. Patient Prefer Adherence. 2016;10:1609-1621.
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