SOHO State of the Art Updates and Next Questions | Beyond BCL-2 Inhibition in Acute Myeloid Leukemia: Other Approaches to Leverage the Apoptotic Pathway

Clinical Lymphoma, Myeloma and Leukemia - Tập 22 - Trang 652-658 - 2022
Abhishek Maiti1, Bing Z. Carter2, Michael Andreeff2, Marina Y. Konopleva2
1Department of Leukemia, University of Texas- MD Anderson Cancer Center, Houston, TX
2Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX

Tài liệu tham khảo

DiNardo, 2020, Azacitidine and venetoclax in previously untreated acute myeloid leukemia, N Engl J Med, 383, 617, 10.1056/NEJMoa2012971 DiNardo, 2021, Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed and relapsed or refractory acute myeloid leukemia, J Clin Oncol, 39, 2768, 10.1200/JCO.20.03736 DiNardo, 2019, Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia, Blood, 133, 7, 10.1182/blood-2018-08-868752 DiNardo, 2020, 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial, Lancet Haematol, 7, e724, 10.1016/S2352-3026(20)30210-6 Chua, 2020, Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (CAVEAT): a phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy, J Clin Oncol, 38, 3506, 10.1200/JCO.20.00572 Lachowiez, 2020, Interim analysis of the phase 1b/2 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, 136, 18, 10.1182/blood-2020-134300 Kadia, 2020, Venetoclax (Ven) added to intensive chemo with cladribine, idarubicin, and AraC (CLIA) achieves high rates of durable complete remission with low rates of measurable residual disease (MRD) in pts with newly diagnosed acute myeloid leukemia (AML), J Clin Oncol, 38 Maiti, 2021, Outcomes of relapsed or refractory acute myeloid leukemia after frontline hypomethylating agent and venetoclax regimens, Haematologica, 106, 894, 10.3324/haematol.2020.252569 Masarova, 2021, Single-center experience with venetoclax combinations in patients with newly diagnosed and relapsed AML evolving from MPNs, Blood Adv, 5, 2156, 10.1182/bloodadvances.2020003934 Nechiporuk, 2019, The TP53 apoptotic network is a primary mediator of resistance to BCL2 inhibition in AML cells, Cancer Discov, 9, 910, 10.1158/2159-8290.CD-19-0125 Kim, 2021, Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax, Cancer, 127, 3772, 10.1002/cncr.33689 Moujalled, 2020, Acquired mutations in BAX confer resistance to BH3 mimetics in acute myeloid leukemia, Blood, 136, 7, 10.1182/blood-2020-136872 Jones, 2020, Nicotinamide metabolism mediates resistance to venetoclax in relapsed acute myeloid leukemia stem cells, Cell Stem Cell [Internet], 10.1016/j.stem.2020.07.021 Stevens, 2020, Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells, Nat Cancer, 1 Pei, 2020, Monocytic subclones confer resistance to venetoclax-based therapy in acute myeloid leukemia patients, Cancer Discov, 10, 536, 10.1158/2159-8290.CD-19-0710 Maiti, 2021, Evolution of genomic landscape in acute myeloid leukemia after decitabine and venetoclax, Blood, 138, 1304, 10.1182/blood-2021-151756 Wilde, 2020, B-cell lymphoma-2 inhibition and resistance in acute myeloid leukemia, World J Clin Oncol, 11, 18, 10.5306/wjco.v11.i8.528 Saliba, 2020, Resistance to venetoclax and hypomethylating agents in acute myeloid leukemia, Cancer Drug Resist [Internet], 10.20517/cdr.2020.95 Saxena, 2020, Harnessing apoptosis in AML, Clin Lymphoma Myeloma Leuk, 20, S61, 10.1016/S2152-2650(20)30464-X Wei, 2020, Targeting MCL-1 in hematologic malignancies: rationale and progress, Blood Rev, 44, 10.1016/j.blre.2020.100672 Choi, 2020, Targeting apoptosis in acute myeloid leukemia: current status and future directions of BCL-2 inhibition with venetoclax and beyond, Target Oncol, 15, 147, 10.1007/s11523-020-00711-3 Roberts, 2021, BCL2 and MCL1 inhibitors for hematologic malignancies, Blood, 138, 1120, 10.1182/blood.2020006785 Thomas, 2013, Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure, Genes Dev, 27, 1365, 10.1101/gad.215871.113 Hasan, 2013, Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1, Development, 140, 3118, 10.1242/dev.090910 Hikita, 2009, Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver, Hepatology, 50, 1217, 10.1002/hep.23126 Luedtke, 2017, 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, 2, 17012, 10.1038/sigtrans.2017.12 Caenepeel, 2018, AMG 176, a selective MCL1 inhibitor, is effective in hematologic cancer models alone and in combination with established therapies, Cancer Discov, 8, 1582, 10.1158/2159-8290.CD-18-0387 Carter, 2021, Maximal activation of apoptosis signaling by co-targeting anti-apoptotic proteins in BH3 mimetic-resistant AML and AML stem cells, Mol Cancer Ther Carter, 2022, Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and re-sensitizes acute myeloid leukemia to BCL-2 inhibition, Haematologica, 107, 58, 10.3324/haematol.2020.260331 Carter, 2020, Co-targeting MCL-1 and BCL-2 is highly synergistic in BH3 Mimetic- and Venetoclax/hypomethylating agent-resistant and TP53 mutated AML, Blood, 136, 7, 10.1182/blood-2020-141417 Carter, 2021, Combined inhibition of Bcl-2 and Mcl-1 circumvents resistance of TP53 deficient/mutant AML to BH3 mimetics, Blood, 138, 2239, 10.1182/blood-2021-148014 Zeidner, 2015, Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia, Haematologica, 100, 1172, 10.3324/haematol.2015.125849 Knorr, 2015, MLN4924 induces Noxa upregulation in acute myelogenous leukemia and synergizes with Bcl-2 inhibitors, Cell Death Differ, 22, 2133, 10.1038/cdd.2015.74 Ochiiwa, 2021, TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia, Oncogene, 40, 1217, 10.1038/s41388-020-01586-4 Takeda provides update on phase 3 PANTHER (Pevonedistat-3001) trial [Internet]. Accessed Jan 10, 2022. Available at: https://www.takeda.com/newsroom/newsreleases/2021/takeda-provides-update-on-phase-3-panther-pevonedistat-3001-trial/ Pan, 2017, Synthetic lethality of combined Bcl-2 inhibition and p53 activation in AML: mechanisms and superior antileukemic efficacy, Cancer Cell, 32, 748, 10.1016/j.ccell.2017.11.003 Rahmani, 2013, Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism, Cancer Res, 73, 1340, 10.1158/0008-5472.CAN-12-1365 Zhou, 2015, Inhibition of Bcl-xL overcomes polyploidy resistance and leads to apoptotic cell death in acute myeloid leukemia cells, Oncotarget, 6, 21557, 10.18632/oncotarget.4306 Lessene, 2013, Structure-guided design of a selective BCL-X L inhibitor, Nat Chem Biol, 9, 390, 10.1038/nchembio.1246 Pullarkat, 2021, Venetoclax and navitoclax in combination with chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma, Cancer Discov, 11, 1440, 10.1158/2159-8290.CD-20-1465 Konopleva, 2006, Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia, Cancer Cell, 10, 375, 10.1016/j.ccr.2006.10.006 Patterson, 2021, Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy, Commun Biol, 4, 112, 10.1038/s42003-020-01631-8 Konopleva, 2021, NIMBLE: a phase I/II study of AZD0466 monotherapy or in combination in patients with advanced hematological malignancies, Blood, 138, 2353, 10.1182/blood-2021-147482 Jia, 2021, Targeting BCL-XL and BCL-2 by protac 753B effectively eliminates AML cells and enhances efficacy of chemotherapy by targeting senescent cells, Blood, 138, 2230, 10.1182/blood-2021-147535 Lv, 2021, Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity, Nat Commun, 12, 6896, 10.1038/s41467-021-27210-x Li, 2021, Inhibitors of BCL2A1/Bfl-1 protein: potential stock in cancer therapy, Eur J Med Chem, 220, 10.1016/j.ejmech.2021.113539 Yamatani, 2021, AML-173: BCL2A1: a novel target in refractory/relapsed AML with FLT3-ITD/D835 double mutations, Clin Lymphoma Myeloma Leuk, 21, S286, 10.1016/S2152-2650(21)01687-6 Liu, 2021, Selective covalent targeting of anti-apoptotic BFL-1 by a sulfonium-tethered peptide, ChemBioChem, 22, 340, 10.1002/cbic.202000473 Harvey, 2020, Identification of a covalent molecular inhibitor of anti-apoptotic BFL-1 by disulfide tethering, Cell Chem Biol, 27, 647, 10.1016/j.chembiol.2020.04.004 Boiko, 2021, Targeting Bfl-1 via acute CDK9 inhibition overcomes intrinsic BH3-mimetic resistance in lymphomas, Blood, 137, 2947, 10.1182/blood.2020008528 Boffo, 2018, CDK9 inhibitors in acute myeloid leukemia, J Exp Clin Cancer Res, 37, 36, 10.1186/s13046-018-0704-8 Garciaz, 2021, Pharmacological reduction of mitochondrial iron triggers a non-canonical BAX/BAK dependent cell death, Cancer Discov [Internet] Salmon, 2018, Combined BCL-2 and HDAC targeting has potent and TP53 independent activity in AML, Blood, 132, 1426, 10.1182/blood-2018-99-117403 Li, 2020, The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia, Haematologica, 106, 1262, 10.3324/haematol.2019.233445 Chua, 2021, An australasian leukemia lymphoma group (ALLG) phase 2 study to investigate novel triplets to extend remission with venetoclax in elderly (INTERVENE) acute myeloid leukemia, Blood, 138, 368, 10.1182/blood-2021-149488 Spitz, 2021, Physiological and pharmacological modulation of BAX, Trends Pharmacol Sci [Internet] Reyna, 2017, Direct activation of BAX by BTSA1 overcomes apoptosis resistance in acute myeloid leukemia, Cancer Cell, 32, 490, 10.1016/j.ccell.2017.09.001 Fulda, 2014, Inhibitor of Apoptosis (IAP) proteins in hematological malignancies: molecular mechanisms and therapeutic opportunities, Leukemia, 28, 1414, 10.1038/leu.2014.56 Schimmer, 2011, Addition of AEG35156 XIAP antisense oligonucleotide in reinduction chemotherapy does not improve remission rates in patients with primary refractory acute myeloid leukemia in a randomized phase II study, Clin Lymphoma Myeloma Leuk, 11, 433, 10.1016/j.clml.2011.03.033 Zhou, 2018, X-linked inhibitor of apoptosis inhibition sensitizes acute myeloid leukemia cell response to TRAIL and chemotherapy through potentiated induction of proapoptotic machinery, Mol Oncol, 12, 33, 10.1002/1878-0261.12146 Hashimoto, 2021, Combined inhibition of XIAP and BCL2 drives maximal therapeutic efficacy in genetically diverse aggressive acute myeloid leukemia, Nat Cancer, 2, 340, 10.1038/s43018-021-00177-w Mita, 2018, Abstract A091: Phase 1 study of IAP inhibitor ASTX660 in adults with advanced cancers and lymphomas, Mol Cancer Ther, 17 Ward, 2018, ASTX660, a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP, potently induces TNFα-dependent apoptosis in cancer cell lines and inhibits tumor growth, Mol Cancer Ther, 17, 1381, 10.1158/1535-7163.MCT-17-0848 Jongen-Lavrencic, 2020, AML-058: first-in-human study of a trail receptor agonist fusion protein, eftozanermin alfa, in patients with relapsed/refractory acute myeloid leukemia and diffuse large B-cell lymphoma, Clin Lymphoma Myeloma Leuk, 20, S177, 10.1016/S2152-2650(20)30708-4 de Jonge, 2019, First-in-human study of abbv-621, a TRAIL receptor agonist fusion protein, in patients (Pts) with relapsed/refractory (RR) acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL), Blood, 134, 10.1182/blood-2019-129783 Richardson, 2020, A phase 1b, open-label study of eftozanermin alfa in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma, Blood, 136, 16, 10.1182/blood-2020-137037 Wang B, Matthew T, Kothambawala T, et al. Agonistic death receptor 5 (DR5) IgM antibody IGM-8444 induces tumor cell apoptosis in vitro and in vivo and has a favorable in vitro safety profile. 1. Jongen-Lavrencic, 2020, First-in-human study of a trail receptor agonist fusion protein, eftozanermin alfa, in patients with relapsed/refractory acute myeloid leukemia and diffuse large b-cell lymphoma [Internet], EHA Library Pipeline – ONK Therapeutics [Internet]. Accessed May 15, 2021; Available at: https://www.onktherapeutics.com/pipeline/ McLornan, 2013, Prognostic and therapeutic relevance of c-FLIP in acute myeloid leukaemia, Br J Haematol, 160, 188, 10.1111/bjh.12108 Supper, 2021, Cut-like homeobox 1 (CUX1) tumor suppressor gene haploinsufficiency induces apoptosis evasion to sustain myeloid leukemia, Nat Commun, 12, 2482, 10.1038/s41467-021-22750-8 Higgins, 2020, Development and preclinical evaluation of unique first-in-class small molecule inhibitors of the anti-apoptotic protein FLIP, AACR, 1 Donehower, 2019, Integrated analysis of TP53 gene and pathway alterations in the cancer genome atlas, Cell Rep, 28, 1370, 10.1016/j.celrep.2019.07.001 Barbosa, 2019, The role of TP53 in acute myeloid leukemia: challenges and opportunities, Genes Chromosomes Cancer, 58, 875, 10.1002/gcc.22796 Konopleva, 2020, MDM2 inhibition: an important step forward in cancer therapy, Leukemia, 34, 2858, 10.1038/s41375-020-0949-z Kojima, 2006, Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia, Blood, 108, 993, 10.1182/blood-2005-12-5148 Andreeff, 2016, Results of the phase I trial of RG7112, a small-molecule MDM2 antagonist in leukemia, Clin Cancer Res, 22, 868, 10.1158/1078-0432.CCR-15-0481 Montesinos, 2020, MIRROS: a randomized, placebo-controlled, phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia, Future Oncol Lond Engl, 16, 807, 10.2217/fon-2020-0044 Daver, 2019, Updated results from the Venetoclax (Ven) in combination with idasanutlin (Idasa) arm of a phase 1b trial in elderly patients (Pts) with relapsed or refractory (R/R) AML ineligible for cytotoxic chemotherapy, Blood, 134, 229, 10.1182/blood-2019-123711 Sabapathy, 2018, Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others, Nat Rev Clin Oncol, 15, 13, 10.1038/nrclinonc.2017.151 Sallman, 2020, The problem of TP53-mutant MDS/AML, Clin Lymphoma Myeloma Leuk, 20, S65, 10.1016/S2152-2650(20)30465-1 2021, Aprea therapeutics announces results of primary endpoint from phase 3 trial of eprenetapopt in TP53 mutant myelodysplastic syndromes (MDS), Aprea Therapeutics [Internet]