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Original Articles

Combination of the dual PIM/PI3-kinase inhibitor IBL-202 and venetoclax is effective in diffuse large B-cell lymphoma

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Pages 3165-3176 | Received 28 Feb 2020, Accepted 04 Jul 2020, Published online: 29 Jul 2020

References

  • Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010;116(12):2040–2045.
  • Reddy A, Zhang J, Davis NS, et al. Genetic and functional drivers of diffuse large B-cell lymphoma. Cell. 2017;171(2):481–494.
  • Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396–1407.
  • van Delft MF, Huang DC. How the Bcl-2 family of proteins interact to regulate apoptosis. Cell Res. 2006;16(2):203–213.
  • Elkholi R, Floros KV, Chipuk JE. The role of BH3-only proteins in tumor cell development, signaling, and treatment. Genes Cancer. 2011;2(5):523–537.
  • Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362(15):1417–1429.
  • Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B-cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679–690.
  • Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390.
  • Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3452–3459.
  • Ye Q, Xu-Monette ZY, Tzankov A, et al. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget. 2016;7(3):2401–2416.
  • Sesques P, Johnson NA. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood. 2017;129(3):280–288.
  • Del Gaizo Moore V, Brown JR, Certo M, et al. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007;117(1):112–121.
  • Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35(8):826–833.
  • Wenzel SS, Grau M, Mavis C, et al. MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma. Leukemia. 2013;27(6):1381–1390.
  • Pan R, Ruvolo VR, Wei J, et al. Inhibition of Mcl-1 with the pan-Bcl-2 family inhibitor (-)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia. Blood. 2015;126(3):363–372.
  • Li L, Pongtornpipat P, Tiutan T, et al. Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1. Leukemia. 2015;29(8):1702–1712.
  • Xu-Monette ZY, Medeiros LJ, Li Y, et al. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood. 2012;119(16):3668–3683.
  • Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274–293.
  • Uddin S, Hussain AR, Siraj AK, et al. Role of phosphatidylinositol 3'-kinase/AKT pathway in diffuse large B-cell lymphoma survival. Blood. 2006;108(13):4178–4186.
  • Choudhary GS, Al-Harbi S, Mazumder S, et al. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015;6:e1593.
  • Lee JS, Tang SS, Ortiz V, et al. MCL-1-independent mechanisms of synergy between dual PI3K/mTOR and BCL-2 inhibition in diffuse large B-cell lymphoma. Oncotarget. 2015;6(34):35202–35217.
  • Pasqualucci L. The genetic basis of diffuse large B-cell lymphoma. Curr Opin Hematol. 2013;20(4):336–344.
  • Brault L, Gasser C, Bracher F, et al. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica. 2010;95(6):1004–1015.
  • Crassini K, Shen Y, O'Dwyer M, et al. The dual inhibitor of the phosphoinositol-3 and PIM kinases, IBL-202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment. Br J Haematol. 2018;182(5):654–669.
  • Gifford G, Gabrielli S, Gill A, et al. Lymphoma cell-of-origin assignment by gene expression profiling is clinically meaningful across broad laboratory contexts. Br J Haematol. 2018;181(2):272–275.
  • Foucquier J, Guedj M. Analysis of drug combinations: current methodological landscape. Pharmacol Res Perspect. 2015;3(3):e00149.
  • Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202–208.
  • Tessoulin B, Papin A, Gomez-Bougie P, et al. BCL2-family dysregulation in B-cell malignancies: from gene expression regulation to a targeted therapy biomarker. Front Oncol. 2018;8:645.
  • Tromp JM, Geest CR, Breij EC, et al. Tipping the Noxa/Mcl-1 balance overcomes ABT-737 resistance in chronic lymphocytic leukemia. Clin Cancer Res. 2012;18(2):487–498.
  • Alves NL, Derks IA, Berk E, et al. The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells. Immunity. 2006;24(6):703–716.
  • Ploner C, Kofler R, Villunger A. Noxa: at the tip of the balance between life and death. Oncogene. 2008;27(Suppl 1):S84–S92.
  • Adams JM, Cory S. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ. 2018;25(1):27–36.
  • Macdonald A, Campbell DG, Toth R, et al. Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. BMC Cell Biol. 2006;7(7):1.
  • Zhang Y, Wang Z, Li X, et al. Pim kinase-dependent inhibition of c-Myc degradation. Oncogene. 2008;27(35):4809–4819.
  • Deng J, Carlson N, Takeyama K, et al. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 2007;12(2):171–185.
  • Pham LV, Huang S, Zhang H, et al. Strategic therapeutic targeting to overcome venetoclax resistance in aggressive B-cell lymphomas. Clin Cancer Res. 2018;24(16):3967–3980.
  • Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–1018.
  • Piddock RE, Bowles KM, Rushworth SA. The role of PI3K isoforms in regulating bone marrow microenvironment signaling focusing on acute myeloid leukemia and multiple myeloma. Cancers (Basel). 2017;9(12):29.
  • Iyengar S, Clear A, Bodor C, et al. P110α-mediated constitutive PI3K signaling limits the efficacy of p110δ-selective inhibition in mantle cell lymphoma, particularly with multiple relapse . Blood. 2013;121(12):2274–2284.
  • Younes A, Salles G, Martinelli G, et al. Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Haematologica. 2017;102(12):2104–2112.
  • Rebello RJ, Huglo AV, Furic L. PIM activity in tumours: a key node of therapy resistance. Adv Biol Regul. 2018;67:163–169.
  • Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer. 2011;11(1):23–34.
  • Mikkers H, Nawijn M, Allen J, et al. Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors. Mol Cell Biol. 2004;24(13):6104–6115.
  • Cortes J, Tamura K, DeAngelo DJ, et al. Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers. Br J Cancer. 2018;118(11):1425–1433.
  • Phillips DC, Xiao Y, Lam LT, et al. Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199). Blood Cancer J. 2015;5:e368.
  • Gandhi L, Camidge DR, Ribeiro de Oliveira M, et al. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011;29(7):909–916.
  • Caenepeel S, Brown SP, Belmontes B, et al. AMG 176, a selective MCL1 inhibitor, is effective in hematologic cancer models alone and in combination with established therapies. Cancer Discov. 2018;8(12):1582–1597.
  • Wang X, Cao X, Sun R, et al. Clinical significance of PTEN deletion, mutation, and loss of PTEN expression in de novo diffuse large B-cell lymphoma. Neoplasia. 2018;20(6):574–593.
  • Pfeifer M, Grau M, Lenze D, et al. PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA. 2013;110(30):12420–12425.

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