Targeting Myc through BET-PROTAC elicits potent anti-lymphoma activity in diffuse large B cell lymphoma

Mafra A, Laversanne M, Gospodarowicz M, Klinger P, Silva NDP, Pineros M et al (2022) Global patterns of non-Hodgkin lymphoma in 2020. Int J Cancer 151(9):1474–1481

Article  CAS  PubMed  Google Scholar 

Wang SS (2023) Epidemiology and etiology of diffuse large B-cell lymphoma. Semin Hematol 60(5):255–266

Article  PubMed  PubMed Central  Google Scholar 

Nastoupil LJ, Bartlett NL (2023) Navigating the evolving treatment landscape of diffuse large B-cell lymphoma. Journal of Clinical Oncology 41(4):903-+

Article  CAS  PubMed  Google Scholar 

Sehn LH, Salles G (2021) Diffuse large B-cell lymphoma. N Engl J Med 384(9):842–858

Article  CAS  PubMed  PubMed Central  Google Scholar 

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390

Article  CAS  PubMed  PubMed Central  Google Scholar 

Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346(4):235–242

Article  CAS  PubMed  Google Scholar 

Crump M, Neelapu SS, Farooq U, Van den Neste E, Kuruvilla J, Westin J et al (2017) Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 130(16):1800–1808

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gisselbrecht C, Glass B, Mounier N, Gill DS, Linch DC, Trneny M et al (2010) Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 28(27):4184–4190

Article  PubMed  PubMed Central  Google Scholar 

Manos K, Chong G, Keane C, Lee S-T, Smith C, Churilov L et al (2023) Immune priming with avelumab and rituximab prior to R-CHOP in diffuse large B-cell lymphoma: the phase II AvR-CHOP study. Leukemia 37(5):1092–1102

Article  CAS  PubMed  Google Scholar 

Vitolo U, Trneny M, Belada D, Burke JM, Carella AM, Chua N et al (2017) Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. Journal of Clinical Oncology. 35(31):3529-+

Article  CAS  PubMed  Google Scholar 

Belada D, Kopeckova K, Burgues JMB, Stevens D, Andre M, Persona EP et al (2023) Safety and efficacy of tafasitamab with or without lenalidomide added to first-line R-CHOP for DLBCL: the phase 1b First-MIND study. Blood 142(16):1348–1358

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trneny M, Sharman JP et al (2022) Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med 386(4):351–363

Article  CAS  PubMed  Google Scholar 

Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J et al (2019) Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. Journal of Clinical Oncology. 37(15):1285-+

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncology 7(5):379–391

Article  CAS  PubMed  Google Scholar 

Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O et al (2011) Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 378(9806):1858–1867

Article  CAS  PubMed  Google Scholar 

Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W et al (2021) ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. Journal of Clinical Oncology. 39(12):1317-+

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G et al (2014) Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncology 15(7):730–737

Article  CAS  PubMed  Google Scholar 

Nowakowski GS, Hong F, Scott DW, Macon WR, King RL, Habermann TM et al (2021) Addition of lenalidomide to R-CHOP improves outcomes in newly diagnosed diffuse large B-cell lymphoma in a randomized phase II US intergroup study ECOG-ACRIN E1412. Journal of Clinical Oncology. 39(12):1329-+

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ott G, Rosenwald A, Campo E (2013) Understanding <i>MYC</i>-driven aggressive B-cell lymphomas: pathogenesis and classification. Blood 122(24):3884–3891

Article  CAS  PubMed  Google Scholar 

Riedell PA, Smith SM (2018) Double hit and double expressors in lymphoma: definition and treatment. Cancer 124(24):4622–4632

Article  PubMed  Google Scholar 

Johnson PWM, Balasubramanian S, Hodkinson B, Shreeve SM, Sun S, Srinivasan S et al (2023) Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL coexpressing BCL2 and MYC in the phase 3 PHOENIX trial. Blood Adv 7(10):2008–2017

Article  CAS  PubMed  PubMed Central  Google Scholar 

Karadkhelkar NM, Lin M, Eubanks LM, Janda KD. Demystifying the druggability of the MYC family of oncogenes. Journal of the American Chemical Society. 2023.

Devaiah BN, Case-Borden C, Gegonne A, Hsu CH, Chen Q, Meerzaman D et al (2016) BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin. Nat Struct Mol Biol 23(6):540–548

Article  CAS  PubMed  PubMed Central  Google Scholar 

Devaiah BN, Mu J, Akman B, Uppal S, Weissman JD, Cheng D et al (2020) MYC protein stability is negatively regulated by BRD4. Proc Natl Acad Sci USA 117(24):13457–13467

Article  CAS  PubMed  PubMed Central  Google Scholar 

Llombart V, Mansour MR. Therapeutic targeting of “undruggable” MYC. Ebiomedicine. 2022;75.

Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K et al (2015) Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chem Biol 22(6):755–763

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sun B, Fiskus W, Qian Y, Rajapakshe K, Raina K, Coleman KG et al (2018) BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells. Leukemia 32(2):343–352

Article  CAS  PubMed  Google Scholar 

del Mar Noblejas-Lopez M, Nieto-Jimenez C, Burgos M, Gomez-Juarez M, Carlos Montero J, Esparis-Ogandow A, et al. Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer. Journal of Experimental & Clinical Cancer Research. 2019;38(1).

Lu Q, Ding X, Huang T, Zhang S, Lu Y, Xu L et al (2019) BRD4 degrader ARV-825 produces long-lasting loss of BRD4 protein and exhibits potent efficacy against cholangiocarcinoma cells. American Journal of Translational Research 11(9):5728–5739

CAS  PubMed  PubMed Central  Google Scholar 

Saenz DT, Fiskus W, Qian Y, Manshouri T, Rajapakshe K, Raina K et al (2017) Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Leukemia 31(9):1951–1961

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu S, Jiang Y, Hong Y, Chu X, Zhang Z, Tao Y, et al. BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting ‘Undruggable’ Myc-pathway genes. Cancer Cell International. 2021;21(1).

Wang ZQ, Zhang ZC, Wu YY, Pi YN, Lou SH, Liu TB et al (2023) Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy. Signal Transduct Target Ther 8(1):420

Comments (0)

No login
gif