Cell cycle inhibitors for the treatment of acute myeloid leukemia: a review of phase 2 & 3 clinical trials

References

• Shallis RM, Wang R, Davidoff A, et al. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70–87.
   PubMed Web of Science ®Google Scholar
• American Cancer Society. Cancer facts & figures 2020. Atlanta, Ga: American Cancer Society; 2020.
   Google Scholar
• Holowiecki J, Grosicki S, Giebel S, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. J Clin Oncol. 2012;30(20):2441–2448.
   PubMed Web of Science ®Google Scholar
• Burnett AK, Russell NH, Hills RK, et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol. 2013;31(27):3360–3368.
   PubMed Web of Science ®Google Scholar
• Borthakur G, Kantarjian H, Wang X, et al. Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer. 2008;113(11):3181–3185.
   PubMed Web of Science ®Google Scholar
• Estey E, Thall P, Andreeff M, et al. Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol. 1994;12(4):671–678.
   PubMed Web of Science ®Google Scholar
• Dickens E, Ahmed S. Principles of cancer treatment by chemotherapy. Surgery. 2018;36(3):134–138.
   Google Scholar
• Di Rora’ AGL, Iacobucci I, Martinelli G. The cell cycle checkpoint inhibitors in the treatment of leukemias. J Hematol Oncol. 2017;10(1):77.
   PubMedGoogle Scholar
• Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454–464.
   PubMed Web of Science ®Google Scholar
• Aboudalle I, Konopleva MY, Kadia TM, et al. A phase Ib/II study of the BCL-2 inhibitor venetoclax in combination with standard intensive AML induction/consolidation therapy with FLAG-IDA in patients with newly diagnosed or relapsed/refractory AML. Blood. 2019;134(Supplement_1):176.
   Google Scholar
• DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17.
   PubMed Web of Science ®Google Scholar
• Borthakur G, Cortes JE, Estey EE, et al. Gemtuzumab ozogamicin with fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG-GO) as front-line regimen in patients with core binding factor acute myelogenous leukemia. Am J Hematol. 2014;89(10):964–968.
   PubMed Web of Science ®Google Scholar
• Boddu P, Gurguis C, Sanford D, et al. Response kinetics and factors predicting survival in core-binding factor leukemia. Leukemia. 2018;32(12):2698–2701.
   PubMed Web of Science ®Google Scholar
• Mills CC, Kolb E, Sampson VB. Development of chemotherapy with cell-cycle inhibitors for adult and pediatric cancer therapy. Cancer Res. 2018;78(2):320–325.
   PubMed Web of Science ®Google Scholar
• Jones AR, Band LR, Murray JA. Double or nothing? Cell division and cell size control. Trends Plant Sci. 2019;24:1083–1093.
   PubMed Web of Science ®Google Scholar
• Dickson MA, Schwartz GK. Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009;16(2):36–43.
   PubMed Web of Science ®Google Scholar
• Oliva EN, Franek J, Patel D, et al. The real-world incidence of relapse in acute myeloid leukemia (AML): a systematic literature review (SLR). Blood. 2018;132(Supplement 1):5188.
   Google Scholar
• Xu J, Lv -T-T, Zhou X-F, et al. Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: A retrospective cohort study. Medicine (Baltimore). 2018;97(39):e12102.
   PubMed Web of Science ®Google Scholar
• Sobhani N, D’Angelo A, Pittacolo M, et al. Updates on the CDK4/6 inhibitory strategy and combinations in breast cancer. Cells. 2019;8(4):321.
   Web of Science ®Google Scholar
• Bailon-Moscoso N, Cevallos-Solorzano G, Romero-Benavides JC, et al. Natural compounds as modulators of cell cycle arrest: application for anticancer chemotherapies. Curr Genomics. 2017;18(2):106–131.
   PubMed Web of Science ®Google Scholar
• Morgan DO. Principles of CDK regulation. Nature. 1995;374(6518):131–134.
   PubMed Web of Science ®Google Scholar
• Satyanarayana A, Kaldis P. Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene. 2009;28(33):2925–2939.
   PubMed Web of Science ®Google Scholar
• Campaner S, Doni M, Hydbring P, et al. Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Nat Cell Biol. 2010;12(1):54–59.
   PubMed Web of Science ®Google Scholar
• Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17(2):93–115.
   PubMed Web of Science ®Google Scholar
• Meloche S, Pouysségur J. The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1-to S-phase transition. Oncogene. 2007;26(22):3227–3239.
   PubMed Web of Science ®Google Scholar
• Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13(12):1501–1512.
   PubMed Web of Science ®Google Scholar
• Indovina P, Giordano A. Targeting the checkpoint kinase WEE1: selective sensitization of cancer cells to DNA-damaging drugs. Cancer Biol Ther. 2010;9(7):523–525.
   PubMed Web of Science ®Google Scholar
• Bavetsias V, Linardopoulos S. Aurora kinase inhibitors: current status and outlook. Front Oncol. 2015;5:278.
   PubMed Web of Science ®Google Scholar
• Dai Y, Grant S. Cyclin-dependent kinase inhibitors. Curr Opin Pharmacol. 2003;3(4):362–370.
   PubMed Web of Science ®Google Scholar
• Uras IZ, Sexl V, Kollmann K. CDK6 inhibition: a novel approach in AML management. Int J Mol Sci. 2020;21(7):2528.
   Web of Science ®Google Scholar
• Carlson BA, Dubay MM, Sausville EA, et al. Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res. 1996;56(13):2973–2978.
   PubMed Web of Science ®Google Scholar
• Zeidner JF, Karp JE. Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia. Leuk Res. 2015;39(12):1312–1318.
   PubMed Web of Science ®Google Scholar
• Melillo G, Sausville EA, Cloud K, et al. Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes. Cancer Res. 1999;59(21):5433–5437.
   PubMed Web of Science ®Google Scholar
• Karp JE, Ross DD, Yang W, et al. Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial. Clin Cancer Res. 2003;9(1):307–315.
   PubMed Web of Science ®Google Scholar
• Karp JE, Passaniti A, Gojo I, et al. Phase I and pharmacokinetic study of flavopiridol followed by 1-β-D-arabinofuranosylcytosine and mitoxantrone in relapsed and refractory adult acute leukemias. Clin Cancer Res. 2005;11(23):8403–8412.
   PubMed Web of Science ®Google Scholar
• Karp JE, Smith BD, Levis MJ, et al. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res. 2007;13(15):4467–4473.
   PubMed Web of Science ®Google Scholar
• Wiernik PH. Alvocidib (flavopiridol) for the treatment of chronic lymphocytic leukemia. Expert Opin Investig Drugs. 2016;25(6):729–734.
   PubMed Web of Science ®Google Scholar
• Zeidner JF, Foster MC, Blackford AL, et al. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+ 3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015;100(9):1172–1179.
   PubMed Web of Science ®Google Scholar
• Boddu P, Kantarjian HM, Garcia-Manero G, et al. Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. Blood Adv. 2017;1(17):1312–1323.
   PubMed Web of Science ®Google Scholar
• Yang X, Zhao X, Phelps MA, et al. A novel liposomal formulation of flavopiridol. Int J Pharm. 2009;365(1):170–174.
   PubMedGoogle Scholar
• Supuran CT. Indisulam: an anticancer sulfonamide in clinical development. Expert Opin Investig Drugs. 2003;12(2):283–287.
   PubMed Web of Science ®Google Scholar
• Bailey KM, Wojtkowiak JW, Hashim AI, et al. Targeting the metabolic microenvironment of tumors. Adv Pharmacol. 2012;65:63–107. Elsevier.
   PubMedGoogle Scholar
• Ozawa Y, Sugi N, Nagasu T, et al. E7070, a novel sulphonamide agent with potent antitumour activity in vitro and in vivo. Eur J Cancer. 2001;37(17):2275–2282.
   PubMed Web of Science ®Google Scholar
• Assi R, Kantarjian HM, Kadia TM, et al. Final results of a phase 2, open‐label study of indisulam, idarubicin, and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high‐risk myelodysplastic syndrome. Cancer. 2018;124(13):2758–2765.
   PubMed Web of Science ®Google Scholar
• Pech MF, Fong LE, Villalta JE, et al. Systematic identification of cancer cell vulnerabilities to natural killer cell-mediated immune surveillance. eLife. 2019;8:e47362.
   PubMed Web of Science ®Google Scholar
• Han T, Goralski M, Gaskill N, et al. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science. 2017;356(6336):eaal3755.
   PubMed Web of Science ®Google Scholar
• Gorlick R, Kolb EA, Houghton PJ, et al. Initial testing (stage 1) of the cyclin dependent kinase inhibitor SCH 727965 (dinaciclib) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012;59(7):1266–1274.
   PubMed Web of Science ®Google Scholar
• Parry D, Guzi T, Shanahan F, et al. Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor. Mol Cancer Ther. 2010;9(8):2344–2353.
   PubMed Web of Science ®Google Scholar
• Gojo I, Sadowska M, Walker A, et al. Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias. Cancer Chemother Pharmacol. 2013;72(4):897–908.
   PubMed Web of Science ®Google Scholar
• Gojo I, Walker A, Cooper M, et al. Phase II study of the cyclin-dependent kinase (CDK) inhibitor dinaciclib (SCH 727965) in patients with advanced acute leukemias. Blood. 2010;116(21):3287.
   Web of Science ®Google Scholar
• Verma S, Bartlett CH, Schnell P, et al. Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3). Oncologist. 2016;21(10):1165.
   PubMed Web of Science ®Google Scholar
• Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. 2015;373(3):209–219.
   PubMed Web of Science ®Google Scholar
• Kadia TM, Konopleva MY, Garcia-Manero G, et al. Phase I study of palbociclib alone and in combination in patients with relapsed and refractory (R/R) leukemias. Blood. 2018;132(Supplement 1):4057.
   Google Scholar
• Zhang H, Wilmot B, Bottomly D, et al. Biomarkers predicting venetoclax sensitivity and strategies for venetoclax combination treatment. Blood. 2018;132(Supplement 1):175.
   Google Scholar
• Herrera-Abreu MT, Palafox M, Asghar U, et al. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor–positive breast cancer. Cancer Res. 2016;76(8):2301–2313.
   PubMed Web of Science ®Google Scholar
• Qiu Z, Oleinick NL, Zhang J. ATR/CHK1 inhibitors and cancer therapy. Radiother Oncol. 2018;126(3):450–464.
   PubMed Web of Science ®Google Scholar
• Dai Y, Grant S. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res. 2010;16(2):376–383.
   PubMed Web of Science ®Google Scholar
• David L, Fernandez-Vidal A, Bertoli S, et al. CHK1 as a therapeutic target to bypass chemoresistance in AML. Sci Signal. 2016;9(445):ra90–ra.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hirai H, Iwasawa Y, Okada M, et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther. 2009;8(11):2992–3000.
   PubMed Web of Science ®Google Scholar
• Porter CC, Kim J, Fosmire S, et al. Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a novel therapeutic target in acute myeloid leukemia. Leukemia. 2012;26(6):1266–1276.
   PubMed Web of Science ®Google Scholar
• Tibes R, Bogenberger JM, Chaudhuri L, et al. RNAi screening of the kinome with cytarabine in leukemias. Blood. 2012;119(12):2863–2872.
   PubMed Web of Science ®Google Scholar
• Oza AM, Weberpals JI, Provencher DM, et al. An international, biomarker-directed, randomized, phase II trial of AZD1775 plus paclitaxel and carboplatin (P/C) for the treatment of women with platinum-sensitive, TP53 -mutant ovarian cancer. Am Soc Clin Oncol. 2015;33:5506.
   PubMedGoogle Scholar
• Garcia TB, Snedeker JC, Baturin D, et al. A small-molecule inhibitor of WEE1, AZD1775, synergizes with olaparib by impairing homologous recombination and enhancing DNA damage and apoptosis in acute leukemia. Mol Cancer Ther. 2017;16(10):2058–2068.
   PubMed Web of Science ®Google Scholar
• Dai Y, Zhou L, Zhang Y, et al. HDAC inhibitors reciprocally interacts the wee1 inhibitor AZD1775 to abrogate both the G1/S and G2/M checkpoints via chk1-related cdc2/Cdk1 threonine 14 dephosphorylation in AML cells. Washington, DC: American Society of Hematology; 2014.
   Google Scholar
• Qi W, Xu X, Wang M, et al. Inhibition of Wee1 sensitizes AML cells to ATR inhibitor VE-822-induced DNA damage and apoptosis. Biochem Pharmacol. 2019;164:273–282.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Ducat D, Zheng Y. Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res. 2004;301(1):60–67.
   PubMed Web of Science ®Google Scholar
• Kantarjian HM, Martinelli G, Jabbour EJ, et al. Stage I of a phase 2 study assessing the efficacy, safety, and tolerability of barasertib (AZD1152) versus low‐dose cytosine arabinoside in elderly patients with acute myeloid leukemia. Cancer. 2013;119(14):2611–2619.
   PubMed Web of Science ®Google Scholar
• Goldberg SL, Fenaux P, Craig MD, et al. An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes. Leuk Res Rep. 2014;3(2):58–61.
   PubMedGoogle Scholar
• Piszczatowski RT, Steidl U. Aurora kinase a inhibition: a mega-hit for myelofibrosis therapy? Clin Cancer Res. 2019;25(16):4868–4870.
   PubMed Web of Science ®Google Scholar
• Gangat N, Marinaccio C, Swords R, et al. Aurora kinase a inhibition provides clinical benefit, normalizes megakaryocytes, and reduces bone marrow fibrosis in patients with myelofibrosis: a Phase I trial. Clin Cancer Res. 2019;25(16):4898.
   PubMed Web of Science ®Google Scholar
• Brunner AM, Blonquist TM, DeAngelo DJ, et al. Phase II clinical trial of alisertib, an Aurora A kinase inhibitor, in combination with induction chemotherapy in high-risk, untreated patients with acute myeloid leukemia. Blood. 2018;132(Supplement 1):766.
   PubMedGoogle Scholar
• Brunner AM, Blonquist TM, DeAngelo DJ, et al. Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial. Lancet Haematol. 2020;7(2):e122–e33.
   PubMed Web of Science ®Google Scholar
• Maiti A, Kantarjian HM, Popat V, et al. Clinical value of event-free survival in acute myeloid leukemia. Blood Adv. 2020;4(8):1690–1699.
   PubMed Web of Science ®Google Scholar