265
Views
0
CrossRef citations to date
0
Altmetric
Review

Investigational CHK1 inhibitors in early stage clinical trials for acute myeloid leukemia

& ORCID Icon
Pages 661-666 | Received 26 Feb 2018, Accepted 30 Jul 2018, Published online: 07 Aug 2018

References

  • Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–1152.
  • SEER Cancer Stat Facts: Acute Myeloid Leukemia. National Cancer Institute. Bethesda, MD. Available from: [cited 2018 Jan 5th]. http://seer.cancer.gov/statfacts/html/amyl.html
  • Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405.
  • NCCN Clinical Practice Guidlines in oncology. Acute Myeloid Leukemia. 2018;V2: MS28–32.
  • Stone RM, Larson RA, Dohner H. Midostaurin in FLT3-mutated acute myeloid leukemia. N Engl J Med. 2017;377(19):1903.
  • Stein EM, Altman JK, Collins R, et al. AG-221, an oral, selective, first-in-class, potent inhibitor of the IDH2 mutant metabolic enzyme, induces durable remissions in a phase i study in patients with IDH2 mutation positive advanced hematologic malignancies. Blood. 2014;124:21.
  • Castaigne S, Pautas C, Terre C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012;379(9825):1508–1516.
  • Lancet JE, Uy GL, Cortes JE, et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016;34:15.
  • Poon RY. Cell cycle control: a system of interlinking oscillators. Methods Mol Biol. 2016;1342:3–19.
  • Esposito MT, So CW. DNA damage accumulation and repair defects in acute myeloid leukemia: implications for pathogenesis, disease progression, and chemotherapy resistance. Chromosoma. 2014;123(6):545–561.
  • Cowell IG, Sondka Z, Smith K, et al. Model for MLL translocations in therapy-related leukemia involving topoisomerase IIbeta-mediated DNA strand breaks and gene proximity. Proc Natl Acad Sci U S A. 2012;109(23):8989–8994.
  • Kushner BH, Heller G, Cheung NK, et al. High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors. J Clin Oncol. 1998;16(9):3016–3020.
  • Stanulla M, Wang J, Chervinsky DS, et al. Topoisomerase II inhibitors induce DNA double-strand breaks at a specific site within the AML1 locus. Leukemia. 1997;11(4):490–496.
  • David L, Fernandez-Vidal A, Bertoli S, et al. CHK1 as a therapeutic target to bypass chemoresistance in AML. Sci Signal. 2016; 9(445).
  • Santamaria C, Chillon MC, Garcia-Sanz R, et al. BAALC is an important predictor of refractoriness to chemotherapy and poor survival in intermediate-risk acute myeloid leukemia (AML). Ann Hematol. 2010;89(5):453–458.
  • Heuser M, Beutel G, Krauter J, et al. High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood. 2006;108(12):3898–3905.
  • Hermkens MC, van den Heuvel-Eibrink MM, Arentsen-Peters ST, et al. The clinical relevance of BAALC and ERG expression levels in pediatric AML. Leukemia. 2013;27(3):735–737.
  • Di Tullio A, Rouault-Pierre K, Abarrategi A, et al. The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia. Nat Commun. 2017; 8.
  • Schenk EL, Koh BD, Flatten KS, et al. Effects of selective checkpoint kinase 1 inhibition on cytarabine cytotoxicity in acute myelogenous leukemia cells in vitro. Clin Cancer Res. 2012;18(19):5364–5373.
  • Yuan LL, Green A, David L, et al. Targeting CHK1 inhibits cell proliferation in FLT3-ITD positive acute myeloid leukemia. Leuk Res. 2014;38(11):1342–1349.
  • Dai Y, Chen S, Kmieciak M, et al. The novel Chk1 inhibitor MK-8776 sensitizes human leukemia cells to HDAC inhibitors by targeting the intra-S checkpoint and DNA replication and repair. Mol Cancer Ther. 2013;12(6):878–889.
  • Zhao JY, 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.
  • Cavelier C, Didier C, Prade N, et al. Constitutive activation of the DNA damage signaling pathway in acute myeloid leukemia with complex karyotype: potential importance for checkpoint targeting therapy. Cancer Res. 2009;69(22):8652–8661.
  • Akiyama T, Yoshida T, Sujita T, et al. G1 phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitor p21/Cip1/WAF1/Sdi1 in p53-mutated human epidermoid carcinoma A431 cells. Cancer Res. 1997;57(8):1495–1501.
  • Komander D, Kular GS, Bain J, et al. Structural basis for UCN-01 (7-hydroxystaurosporine) specificity and PDK1 (3-phosphoinositide-dependent protein kinase-1) inhibition. Biochem J. 2003;375:255–262.
  • Matthews DJ, Yakes FM, Chen J, et al. Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle. 2007;6(1):104–110.
  • Sha SK, Sato T, Kobayashi H, et al. Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint. Mol Cancer Ther. 2007;6(1):147–153.
  • Fuse E, Tanii H, Kurata N, et al. Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alpha1-acid glycoprotein. Cancer Res. 1998;58(15):3248–3253.
  • Sampath D, Cortes J, Estrov Z, et al. Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood. 2006;107(6):2517–2524.
  • Koniaras K, Cuddihy AR, Christopoulos H, et al. Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells. Oncogene. 2001;20(51):7453–7463.
  • Reinhardt HC, Aslanian AS, Lees JA, et al. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell. 2007;11(2):175–189.
  • Zenvirt S, Kravchenko-Balasha N, Levitzki A. Status of p53 in human cancer cells does not predict efficacy of CHK1 kinase inhibitors combined with chemotherapeutic agents. Oncogene. 2010;29(46):6149–6159.
  • Welch S, Hirte HW, Carey MS, et al. UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital phase II consortium. Gynecol Oncol. 2007;106(2):305–310.
  • Ma CX, Mj E, Petroni GR, et al. A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res Treat. 2013;137(2):483–492.
  • Guzi TJ, Paruch K, Dwyer MP, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011;10(4):591–602.
  • Montano R, Chung I, Garner KM, et al. Preclinical development of the Novel Chk1 Inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites. Mol Cancer Ther. 2012;11(2):427–438.
  • Karp JE, Thomas BM, Greer JM, et al. Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias. Clin Cancer Res. 2012;18(24):6723–6731.
  • Webster JA, Tibes R, Morris L, et al. Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia. Leuk Res. 2017;61:108–116.
  • King C, Diaz H, Barnard D, et al. Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014;32(2):213–226.
  • Marshall M, Barda D, Barnard D, et al. Characterization and preclinical development of LCI-1, a selective and potent Chk1 inhibitor in phase 1 clinical trials. Mol Cancer Ther. 2009;8(12).
  • Sarmento LM, Povoa V, Nascimento R, et al. CHK1 overexpression in T-cell acute lymphoblastic leukemia is essential for proliferation and survival by preventing excessive replication stress. Oncogene. 2015;34(23):2978–2990.
  • Iacobucci I, Di Rora AG, Falzacappa MV, et al. In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia. J Hematol Oncol. 2015; 8.
  • Nguyen T, Hawkins E, Kolluri, et al. Synergism between bosutinib (SKI-606) and the Chk1 inhibitor (PF-00477736) in highly imatinib-resistant BCR/ABL(+) leukemia cells. Leuk Res. 2015;39(1):65–71.
  • Didier C, Demur C, Grimal F, et al. Evaluation of checkpoint kinase targeting therapy in acute myeloid leukemia with complex karyotype. Cancer Biol Ther. 2012;13(5):307–313.
  • Landau HJ, McNeely SC, Nair JS, et al. The checkpoint kinase Inhibitor AZD7762 potentiates chemotherapy-induced apoptosis of p53-mutated multiple myeloma cells. Mol Cancer Ther. 2012;11(8):1781–1788.
  • Hong D, Infante J, Janku F, et al. Phase I study of LY2606368, a checkpoint Kinase 1 inhibitor in patients with advanced cancer. J Clin Oncol. 2016;34(15):1764–1771.
  • King C, Diaz HB, McNeely S, et al. LY2606368 causes replication catastrophe and antitumor effects through CHK1-dependent mechanisms. Mol Cancer Ther. 2015;14(9):2004–2013.
  • Di Rora AGL, Iacobucci I, Imbrogno E, et al. Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia. Oncotarget. 2016;7(33):53377–53391.
  • Josse R, Martin SE, Guha R, et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase I inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014;74(23):6968–6979.
  • Hall AB, Newsome D, Wang Y, et al. Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970. Oncotarget. 2014;5(14):5674–5685.
  • Vavrova J, Zarybnicka L, Lukasova E, et al. Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60). Radiat Environ Biophys. 2013;52(4):471–479.
  • Menezes DL, Holt J, Tang Y, et al. A synthetic lethal screen reveals enhanced sensitivity to ATR inhibitor treatment in mantle cell lymphoma with ATM loss-of-Function. Mol Cancer Res. 2015;13(1):120–129.
  • Kwok M, Davies N, Agathanggelou A, et al. Synthetic lethality in chronic lymphocytic leukaemia with DNA damage response defects by targeting the ATR pathway. Lancet. 2015;385:58.
  • Zhou L, Zhang Y, Chen S, et al. A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations. Leukemia. 2015;29(4):807–818.
  • Chaudhuri L, Vincelette ND, Koh BD, et al. CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivo. Haematologica. 2014;99(4):688–696.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.