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image of The EP300-Targeting Drug CCS1477 Inhibits the Growth and Development ofDiffuse Large B-Cell Lymphoma by Promoting Apoptosis and Mitophagy to Reduce Drug Resistance

Abstract

Introduction

Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) develop primary resistance or relapse, owing to the high heterogeneity and aggressive nature of the disease. Consequently, novel drugs are urgently needed to improve outcomes in patients who are resistant.

Methods

This study quantified the anti-proliferative effects of CCS1477 using the Cell Counting Kit-8 assay, 5‐ethynyl‐2′‐deoxyuridine staining, and lactate dehydrogenase measurement. Flow cytometry and Western blot analyses were performed concurrently to investigate the induction of apoptosis and the activation of mitophagy. The efficacy and safety of CCS1477 were evaluated in models. To elucidate the mechanism, cell lines with EP300 knockdown and overexpression were established. Functional assays and Western blot analyses revealed that EP300 regulates apoptosis, mitophagy, and c-MYC-mediated drug-resistant phenotypes.

Results

This study demonstrated that CCS1477, a highly selective EP300/CBP bromodomain inhibitor, significantly suppressed the progression of diffuse large B-cell lymphoma. The study revealed that CCS1477 dose-dependently inhibited the proliferation of diffuse large B-cell lymphoma cells and induced apoptosis and mitophagy. Mechanistically, EP300 downregulation promoted apoptosis and activated the PINK1-dependent mitophagy pathway while suppressing c-MYC-mediated drug resistance genes, ultimately inhibiting DLBCL cell proliferation. In animal models, CCS1477 significantly reduced tumor volume and extended doubling time, providing the first evidence of its antitumor activity against DLBCL.

Discussion

Through systematic and investigations, this study validated the significant therapeutic promise of EP300/CBP inhibitor CCS1477 for diffuse large B-cell lymphoma. However, the mechanistic basis for differential sensitivity across DLBCL subtypes, along with long-term efficacy and potential adverse effects, requires comprehensive investigation. Notably, EP300 has been verified as a novel prognostic biomarker and therapeutic target; this work establishes an innovative epigenetic-targeted strategy for relapsed/refractory diffuse large B-cell lymphoma.

Conclusion

By selectively targeting EP300, CCS1477 orchestrates a dual pro-death mechanism involving both intrinsic apoptosis execution and PINK1-driven mitochondrial clearance, resulting in significant inhibition of diffuse large B-cell lymphoma pathogenesis.

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2025-10-10
2025-11-07

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References

  1. Silkenstedt E. Salles G. Campo E. Dreyling M. B-cell non-Hodgkin lymphomas. Lancet 2024 403 10438 1791 1807 10.1016/S0140‑6736(23)02705‑8 38614113
    [Google Scholar]
  2. Armitage J.O. Gascoyne R.D. Lunning M.A. Cavalli F. Non-Hodgkin lymphoma. Lancet 2017 390 10091 298 310 10.1016/S0140‑6736(16)32407‑2 28153383
    [Google Scholar]
  3. Alduaij W. Collinge B. Ben-Neriah S. Jiang A. Hilton L.K. Boyle M. Meissner B. Chong L. Miyata-Takata T. Slack G.W. Farinha P. Craig J.W. Lytle A. Savage K.J. Villa D. Gerrie A.S. Freeman C.L. Gascoyne R.D. Connors J.M. Morin R.D. Sehn L.H. Mungall A.J. Steidl C. Scott D.W. Molecular determinants of clinical outcomes in a real-world diffuse large B-cell lymphoma population. Blood 2023 141 20 2493 2507 36302166
    [Google Scholar]
  4. Moffitt A.B. Dave S.S. Clinical applications of the genomic landscape of aggressive non-Hodgkin Lymphoma. J. Clin. Oncol. 2017 35 9 955 962 10.1200/JCO.2016.71.7603 28297626
    [Google Scholar]
  5. Alizadeh A.A. Eisen M.B. Davis R.E. Ma C. Lossos I.S. Rosenwald A. Boldrick J.C. Sabet H. Tran T. Yu X. Powell J.I. Yang L. Marti G.E. Moore T. Hudson J. Lu L. Lewis D.B. Tibshirani R. Sherlock G. Chan W.C. Greiner T.C. Weisenburger D.D. Armitage J.O. Warnke R. Levy R. Wilson W. Grever M.R. Byrd J.C. Botstein D. Brown P.O. Staudt L.M. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000 403 6769 503 511 10.1038/35000501 10676951
    [Google Scholar]
  6. Carbone A. Younes A. Lymphomas and microenvironment: Impact on lymphomagenesis. Semin. Cancer Biol. 2015 34 1 2 10.1016/j.semcancer.2015.05.001 26026591
    [Google Scholar]
  7. Shingleton J. Wang J. Baloh C. Dave T. Davis N. Happ L. Jadi O. Kositsky R. Li X. Love C. Panea R. Qin Q. Reddy A. Singhi N. Smith E. Thakkar D. Dave S.S. Non-hodgkin lymphomas: Malignancies arising from mature b cells. Cold Spring Harb. Perspect. Med. 2021 11 3 a034843 10.1101/cshperspect.a034843 32152246
    [Google Scholar]
  8. Elenitoba-Johnson K.S.J. Lim M.S. New insights into lymphoma pathogenesis. Annu. Rev. Pathol. 2018 13 1 193 217 10.1146/annurev‑pathol‑020117‑043803 29140757
    [Google Scholar]
  9. Liu Y. Barta S.K. Diffuse large B‐cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am. J. Hematol. 2019 94 5 604 616 10.1002/ajh.25460 30859597
    [Google Scholar]
  10. Hilton L.K. Scott D.W. Morin R.D. Biological heterogeneity in diffuse large B-cell lymphoma. Semin. Hematol. 2023 60 5 267 276 10.1053/j.seminhematol.2023.11.006 38151380
    [Google Scholar]
  11. Yue N. Jin Q. Li C. Zhang L. Cao J. Wu C. Recent advances in CD5+ diffuse large B-cell lymphoma. Ann. Hematol. 2024 103 11 4401 4412 10.1007/s00277‑024‑05974‑8 39196380
    [Google Scholar]
  12. Rosenthal A. Younes A. High grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6: Double hit and triple hit lymphomas and double expressing lymphoma. Blood Rev. 2017 31 2 37 42 10.1016/j.blre.2016.09.004 27717585
    [Google Scholar]
  13. Künstner A. Witte H.M. Riedl J. Bernard V. Stölting S. Merz H. Olschewski V. Peter W. Ketzer J. Busch Y. Trojok P. Bubnoff N. Busch H. Feller A.C. Gebauer N. Mutational landscape of high-grade B-cell lymphoma with MYC-, BCL2 and/or BCL6 rearrangements characterized by whole-exome sequencing. Haematologica 2021 107 8 1850 1863 10.3324/haematol.2021.279631 34788985
    [Google Scholar]
  14. Witte H.M. Riedl J. Künstner A. Fähnrich A. Ketzer J. Fliedner S.M.J. Reimer N. Bernard V. von Bubnoff N. Merz H. Busch H. Feller A. Gebauer N. Molecularly stratified treatment options in primary refractory DLBCL/HGBL with MYC and BCL2 or BCL6 rearrangements (HGBL, NOS with MYC/BCL6). Target. Oncol. 2023 18 5 749 765 10.1007/s11523‑023‑00983‑5 37488307
    [Google Scholar]
  15. Rodríguez-Pinilla S.M. Santonja C. Stewart P. Carvajal N. McCafferty N. Manso R. Meizoso T. Caro Gutiérrez M.D. Piris M.Á. González de Castro D. Indolent clinical behaviour of primary cutaneous diffuse large B‐cell lymphoma, leg type, with double MYC and BCL6 gene rearrangement. Br. J. Haematol. 2020 191 3 e83 e86 10.1111/bjh.17038 32780869
    [Google Scholar]
  16. Alabdaljabar M.S. Durani U. Thompson C.A. Constine L.S. Hashmi S.K. The forgotten survivor: A comprehensive review on Non‐Hodgkin lymphoma survivorship. Am. J. Hematol. 2022 97 12 1627 1637 10.1002/ajh.26719 36069675
    [Google Scholar]
  17. Nastoupil L.J. Bartlett N.L. Navigating the evolving treatment landscape of diffuse large b-cell lymphoma. J. Clin. Oncol. 2023 41 4 903 913 10.1200/JCO.22.01848 36508700
    [Google Scholar]
  18. Ansell S.M. Lin Y. Immunotherapy of lymphomas. J. Clin. Invest. 2020 130 4 1576 1585 10.1172/JCI129206 32039913
    [Google Scholar]
  19. Schroers-Martin J.G. Alig S. Garofalo A. Tessoulin B. Sugio T. Alizadeh A.A. Molecular monitoring of lymphomas. Annu. Rev. Pathol. 2023 18 1 149 180 10.1146/annurev‑pathol‑050520‑044652 36130071
    [Google Scholar]
  20. Donati G. Ravà M. Filipuzzi M. Nicoli P. Cassina L. Verrecchia A. Doni M. Rodighiero S. Parodi F. Boletta A. Vellano C.P. Marszalek J.R. Draetta G.F. Amati B. Targeting mitochondrial respiration and the BCL2 family in high‐grade MYC‐associated B‐cell lymphoma. Mol. Oncol. 2022 16 5 1132 1152 10.1002/1878‑0261.13115 34632715
    [Google Scholar]
  21. Sermer D. Bobillo S. Dogan A. Zhang Y. Seshan V. Lavery J.A. Batlevi C. Caron P. Hamilton A. Hamlin P. Horwitz S. Joffe E. Kumar A. Matasar M. Noy A. Owens C. Moskowitz A. Palomba M.L. Straus D. von Keudell G. Rodriguez-Rivera I. Falchi L. Zelenetz A. Yahalom J. Younes A. Extra copies of MYC, BCL2, and BCL6 and outcome in patients with diffuse large B-cell lymphoma. Blood Adv. 2020 4 14 3382 3390 10.1182/bloodadvances.2020001551 32722781
    [Google Scholar]
  22. Zhang J. Weng Z. Huang Y. Li M. Wang F. Wang Y. Rao H. High-grade B-cell Lymphoma With MYC, BCL2, and/or BCL6 translocations/rearrangements. Am. J. Surg. Pathol. 2020 44 12 1602 1611 10.1097/PAS.0000000000001577 32991338
    [Google Scholar]
  23. Choe J.Y. Park M. Yun J.Y. Na H.Y. Go H. Kim H.J. Oh S. Kim J.E. PELI1 expression is correlated with MYC and BCL6 expression and associated with poor prognosis in diffuse large B-cell lymphoma. Mod. Pathol. 2016 29 11 1313 1323 10.1038/modpathol.2016.128 27469333
    [Google Scholar]
  24. Sermer D. Pasqualucci L. Wendel H.G. Melnick A. Younes A. Emerging epigenetic-modulating therapies in lymphoma. Nat. Rev. Clin. Oncol. 2019 16 8 494 507 10.1038/s41571‑019‑0190‑8 30837715
    [Google Scholar]
  25. Goel R.R. Rook A.H. Immunobiology and treatment of cutaneous T-cell lymphoma. Expert Rev. Clin. Immunol. 2024 20 8 985 996 10.1080/1744666X.2024.2326035 38450476
    [Google Scholar]
  26. Bouroumeau A. Bussot L. Bonnefoix T. Fournier C. Chapusot C. Casasnovas O. Martin L. McLeer A. Col E. David-Boudet L. Lefebvre C. Algrin C. Raskovalova T. Jacob M.C. Vettier C. Chevalier S. Callanan M.B. Gressin R. Emadali A. Sartelet H. c‐MYC and p53 expression highlight starry‐sky pattern as a favourable prognostic feature in R‐CHOP ‐treated diffuse large B‐cell lymphoma. J. Pathol. Clin. Res. 2021 7 6 604 615 10.1002/cjp2.223 34374220
    [Google Scholar]
  27. Smyth E. Cheah C.Y. Seymour J.F. Management of indolent B-cell Lymphomas: A review of approved and emerging targeted therapies. Cancer Treat. Rev. 2023 113 102510 10.1016/j.ctrv.2023.102510 36634434
    [Google Scholar]
  28. Klener P. Klanova M. Drug resistance in non-hodgkin lymphomas. Int. J. Mol. Sci. 2020 21 6 2081 10.3390/ijms21062081 32197371
    [Google Scholar]
  29. Cassanello G. Luna de Abia A. Falchi L. Trial watch: Bispecific antibodies for the treatment of relapsed or refractory large B-cell lymphoma. OncoImmunology 2024 13 1 2321648 10.1080/2162402X.2024.2321648 38445082
    [Google Scholar]
  30. Villacampa G. Dienstmann R. Bosch F. Abrisqueta P. Combination of novel molecular targeted agent plus R-CHOP-based regimen versus R-CHOP alone in previously untreated diffuse large B-cell lymphoma (DLBCL) patients: A systematic review and meta-analysis. Ann. Hematol. 2021 100 12 2969 2978 10.1007/s00277‑021‑04623‑8 34378095
    [Google Scholar]
  31. Sinkarevs S. Strumfs B. Volkova S. Strumfa I. Tumour microenvironment: The general principles of pathogenesis and implications in diffuse large b cell lymphoma. Cells 2024 13 12 1057 10.3390/cells13121057 38920685
    [Google Scholar]
  32. Cai Q. Westin J. Fu K. Desai M. Zhang L. Huang H. Jiang W. Liang R. Qian Z. Champlin R.E. Wang M. Accelerated therapeutic progress in diffuse large B cell lymphoma. Ann. Hematol. 2014 93 4 541 556 10.1007/s00277‑013‑1979‑7 24375125
    [Google Scholar]
  33. Sesques P. Johnson N.A. 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 10.1182/blood‑2016‑02‑636316 27821509
    [Google Scholar]
  34. Wei W. Song Z. Chiba M. Wu W. Jeong S. Zhang J.P. Kadin M.E. Nakagawa M. Yang Y. Analysis and therapeutic targeting of the EP300 and CREBBP acetyltransferases in anaplastic large cell lymphoma and Hodgkin lymphoma. Leukemia 2023 37 2 396 407 10.1038/s41375‑022‑01774‑z 36456744
    [Google Scholar]
  35. Manson G. Houot R. Next-generation immunotherapies for lymphoma: One foot in the future. Ann. Oncol. 2018 29 3 588 601 10.1093/annonc/mdy032 29365060
    [Google Scholar]
  36. Sawalha Y. Maddocks K. Novel treatments in B cell non-Hodgkin’s lymphomas. BMJ 2022 377 063439 10.1136/bmj‑2020‑063439 35443983
    [Google Scholar]
  37. Wu X. Zhang X. Tang S. Wang Y. The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors. Cell Biol. Toxicol. 2025 41 1 32 10.1007/s10565‑024‑09984‑0 39825161
    [Google Scholar]
  38. Nicosia L. Spencer G.J. Brooks N. Amaral F.M.R. Basma N.J. Chadwick J.A. Revell B. Wingelhofer B. Maiques-Diaz A. Sinclair O. Camera F. Ciceri F. Wiseman D.H. Pegg N. West W. Knurowski T. Frese K. Clegg K. Campbell V.L. Cavet J. Copland M. Searle E. Somervaille T.C.P. Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies. Cancer Cell 2023 41 12 2136 2153.e13 10.1016/j.ccell.2023.11.001 37995682
    [Google Scholar]
  39. White J. Derheimer F.A. Jensen-Pergakes K. O’Connell S. Sharma S. Spiegel N. Paul T.A. Histone lysine acetyltransferase inhibitors: An emerging class of drugs for cancer therapy. Trends Pharmacol. Sci. 2024 45 3 243 254 10.1016/j.tips.2024.01.010 38383216
    [Google Scholar]
  40. Dutta R. Tiu B. Sakamoto K.M. CBP/p300 acetyltransferase activity in hematologic malignancies. Mol. Genet. Metab. 2016 119 1-2 37 43 10.1016/j.ymgme.2016.06.013 27380996
    [Google Scholar]
  41. Lunning M.A. Green M.R. Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas. Blood Cancer J. 2015 5 10 361 10.1038/bcj.2015.89 26473533
    [Google Scholar]
  42. Zeng Q. Wang K. Zhao Y. Ma Q. Chen Z. Huang W. Effects of the acetyltransferase p300 on tumour regulation from the novel perspective of posttranslational protein modification. Biomolecules 2023 13 3 417 10.3390/biom13030417 36979352
    [Google Scholar]
  43. Ebrahimi A. Waha A. Schittenhelm J. Gohla G. Schuhmann M.U. Pietsch T. BCOR:CREBBP fusion in malignant neuroepithelial tumor of CNS expands the spectrum of methylation class CNS tumor with BCOR/BCOR(L1)-fusion. Acta Neuropathol. Commun. 2024 12 1 60 10.1186/s40478‑024‑01780‑5 38637838
    [Google Scholar]
  44. Chang Q. Li J. Deng Y. Zhou R. Wang B. Wang Y. Zhang M. Huang X. Li Y. Discovery of novel PROTAC degraders of p300/CBP as potential therapeutics for hepatocellular carcinoma. J. Med. Chem. 2024 67 4 2466 2486 10.1021/acs.jmedchem.3c01468 38316017
    [Google Scholar]
  45. Dutto I. Scalera C. Prosperi E. CREBBP and p300 lysine acetyl transferases in the DNA damage response. Cell. Mol. Life Sci. 2018 75 8 1325 1338 10.1007/s00018‑017‑2717‑4 29170789
    [Google Scholar]
  46. Vlasevska S. Garcia-Ibanez L. Duval R. Holmes A.B. Jahan R. Cai B. Kim A. Mo T. Basso K. Soni R.K. Bhagat G. Dalla-Favera R. Pasqualucci L. KMT2D acetylation by CREBBP reveals a cooperative functional interaction at enhancers in normal and malignant germinal center B cells. Proc. Natl. Acad. Sci. USA 2023 120 11 2218330120 10.1073/pnas.2218330120 36893259
    [Google Scholar]
  47. Kumar E.A. Korfi K. Bewicke-Copley F. Close K. Heward J. Witzig T. Leukam M. Ansell S. Scott J. Clear A. Efeyan A. Green M. Siebert R. Peck B. Calaminici M. Wang J. Smith S. Novak A. Fitzgibbon J. Okosun J. CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma. Br. J. Haematol. 2024 205 5 1804 1809 10.1111/bjh.19671 39188028
    [Google Scholar]
  48. Garcia-Gimenez A. Ditcham J.E. Azazi D.M.A. Giotopoulos G. Asby R. Meduri E. Bagri J. Sakakini N. Lopez C.K. Narayan N. Beinortas T. Agrawal-Singh S. Fung K. O’Connor D. Mansour M.R. Alabed H.B.R. Jenkins B. Koulman A. Murphy M.P. Horton S.J. Huntly B.J.P. Richardson S.E. CREBBP inactivation sensitizes B cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition. Nat. Commun. 2025 16 1 4274 10.1038/s41467‑025‑59531‑6 40393984
    [Google Scholar]
  49. Zhang Q. Song Y. Zhou K. Lin Q. Emerging therapeutic agents in multiple myeloma: Highlights from the 2024 ASH annual meeting. Biomark. Res. 2025 13 1 90 10.1186/s40364‑025‑00803‑0 40597448
    [Google Scholar]
  50. Welti J. Sharp A. Brooks N. Yuan W. McNair C. Chand S.N. Pal A. Figueiredo I. Riisnaes R. Gurel B. Rekowski J. Bogdan D. West W. Young B. Raja M. Prosser A. Lane J. Thomson S. Worthington J. Onions S. Shannon J. Paoletta S. Brown R. Smyth D. Harbottle G.W. Gil V.S. Miranda S. Crespo M. Ferreira A. Pereira R. Tunariu N. Carreira S. Neeb A.J. Ning J. Swain A. Taddei D. Schiewer M.J. Knudsen K.E. Pegg N. de Bono J.S. Targeting the p300/CBP axis in lethal prostate cancer. Cancer Discov. 2021 11 5 1118 1137 10.1158/2159‑8290.CD‑20‑0751 33431496
    [Google Scholar]
  51. Chen Z. Wang M. Wu D. Zhao L. Metwally H. Jiang W. Wang Y. Bai L. McEachern D. Luo J. Wang M. Li Q. Matvekas A. Wen B. Sun D. Chinnaiyan A.M. Wang S. Discovery of CBPD-409 as a highly potent, selective, and orally efficacious CBP/p300 PROTAC degrader for the treatment of advanced prostate cancer. J. Med. Chem. 2024 67 7 5351 5372 10.1021/acs.jmedchem.3c01789 38530938
    [Google Scholar]
  52. Rasool R. Natesan R. Asangani I.A. Toppling the HAT to treat lethal prostate cancer. Cancer Discov. 2021 11 5 1011 1013 10.1158/2159‑8290.CD‑21‑0184 33947717
    [Google Scholar]
  53. Sardar S. McNair C.M. Ravindranath L. Chand S.N. Yuan W. Bogdan D. Welti J. Sharp A. Ryan N.K. Knudsen L.A. Schiewer M.J. DeArment E.G. Janas T. Su X.A. Butler L.M. de Bono J.S. Frese K. Brooks N. Pegg N. Knudsen K.E. Shafi A.A. AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer. Oncogene 2024 43 43 3197 3213 10.1038/s41388‑024‑03148‑4 39266679
    [Google Scholar]
  54. Donati G. Nicoli P. Verrecchia A. Vallelonga V. Croci O. Rodighiero S. Audano M. Cassina L. Ghsein A. Binelli G. Boletta A. Mitro N. Amati B. Oxidative stress enhances the therapeutic action of a respiratory inhibitor in MYC ‐driven lymphoma. EMBO Mol. Med. 2023 15 6 16910 10.15252/emmm.202216910 37158102
    [Google Scholar]
  55. Kanada R. Kagoshima Y. Suzuki T. Nakamura A. Funami H. Watanabe J. Asano M. Takahashi M. Ubukata O. Suzuki K. Aikawa T. Sato K. Goto M. Setsu G. Ito K. Kihara K. Kuroha M. Kohno T. Ogiwara H. Isoyama T. Tominaga Y. Higuchi S. Naito H. Discovery of DS-9300: A highly potent, selective, and once-daily oral EP300/CBP histone acetyltransferase inhibitor. J. Med. Chem. 2023 66 1 695 715 10.1021/acs.jmedchem.2c01641 36572866
    [Google Scholar]
  56. Wilson J.E. Patel G. Patel C. Brucelle F. Huhn A. Gardberg A.S. Poy F. Cantone N. Bommi-Reddy A. Sims R.J. Cummings R.T. Levell J.R. Discovery of CPI-1612: A potent, selective, and orally bioavailable ep300/cbp histone acetyltransferase inhibitor. ACS Med. Chem. Lett. 2020 11 6 1324 1329 10.1021/acsmedchemlett.0c00155 32551019
    [Google Scholar]
  57. Bosnakovski D. da Silva M.T. Sunny S.T. Ener E.T. Toso E.A. Yuan C. Cui Z. Walters M.A. Jadhav A. Kyba M. A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death. Sci. Adv. 2019 5 9 eaaw7781 10.1126/sciadv.aaw7781 31535023
    [Google Scholar]
  58. Zhang J. Vlasevska S. Wells V.A. Nataraj S. Holmes A.B. Duval R. Meyer S.N. Mo T. Basso K. Brindle P.K. Hussein S. Dalla-Favera R. Pasqualucci L. The CREBBP acetyltransferase is a haploinsufficient tumor suppressor in b-cell lymphoma. Cancer Discov. 2017 7 3 322 337 10.1158/2159‑8290.CD‑16‑1417 28069569
    [Google Scholar]
  59. Tontsch-Grunt U. Traexler P.E. Baum A. Musa H. Marzin K. Wang S. Trapani F. Engelhardt H. Solca F. Therapeutic impact of BET inhibitor BI 894999 treatment: Backtranslation from the clinic. Br. J. Cancer 2022 127 3 577 586 10.1038/s41416‑022‑01815‑5 35444289
    [Google Scholar]
  60. Huang Y.H. Cai K. Xu P.P. Wang L. Huang C.X. Fang Y. Cheng S. Sun X.J. Liu F. Huang J.Y. Ji M.M. Zhao W.L. CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis. Signal Transduct. Target. Ther. 2021 6 1 10 10.1038/s41392‑020‑00437‑8 33431788
    [Google Scholar]
  61. Thieme E. Bruss N. Sun D. Dominguez E.C. Coleman D. Liu T. Roleder C. Martinez M. Garcia-Mansfield K. Ball B. Pirrotte P. Wang L. Xia Z. Danilov A.V. CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma. Mol. Cancer 2023 22 1 64 10.1186/s12943‑023‑01762‑6 36998071
    [Google Scholar]
  62. Wang C. Fu W. Zhang Y. Hu X. Xu Q. Tong X. C-MYC-activated lncRNA SNHG20 accelerates the proliferation of diffuse large B cell lymphoma via USP14-mediated deubiquitination of β-catenin. Biol. Direct 2024 19 1 47 10.1186/s13062‑024‑00488‑9 38886753
    [Google Scholar]
  63. Epperla N. Maddocks K.J. Salhab M. Chavez J.C. Reddy N. Karmali R. Umyarova E. Bachanova V. Costa C. Glenn M. Calzada O. Xavier A.C. Zhou Z. Hossain N.M. Hernandez-Ilizaliturri F.J. Al-Mansour Z. Barta S.K. Chhabra S. Lansigan F. Mehta A. Jaglal M.V. Evans A. Flowers C.R. Cohen J.B. Fenske T.S. Hamadani M. Costa L.J. C‐MYC -positive relapsed and refractory, diffuse large B ‐cell lymphoma: Impact of additional “hits” and outcomes with subsequent therapy. Cancer 2017 123 22 4411 4418 10.1002/cncr.30895 28749548
    [Google Scholar]
  64. Esteve-Arenys A. Valero J.G. Chamorro-Jorganes A. Gonzalez D. Rodriguez V. Dlouhy I. Salaverria I. Campo E. Colomer D. Martinez A. Rymkiewicz G. Pérez-Galán P. Lopez-Guillermo A. Roué G. The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma. Oncogene 2018 37 14 1830 1844 10.1038/s41388‑017‑0111‑1 29353886
    [Google Scholar]
  65. Fiskus W. Mill C.P. Perera D. Birdwell C. Deng Q. Yang H. Lara B.H. Jain N. Burger J. Ferrajoli A. Davis J.A. Saenz D.T. Jin W. Coarfa C. Crews C.M. Green M.R. Khoury J.D. Bhalla K.N. BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma. Leukemia 2021 35 9 2621 2634 10.1038/s41375‑021‑01181‑w 33654205
    [Google Scholar]
  66. Li X.Y. Wu J.C. Liu P. Li Z.J. Wang Y. Chen B.Y. Hu C.L. Fei M.Y. Yu P.C. Jiang Y.L. Xu C.H. Chang B.H. Chen X.C. Zong L.J. Zhang J.Y. Fang Y. Sun X.J. Xue K. Wang L. Chen S.B. Jiang S.Y. Gui A. Yang L. Gu J.J. Yu B.H. Zhang Q. Wang L. Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma. Leukemia 2023 37 1 164 177 10.1038/s41375‑022‑01747‑2 36352191
    [Google Scholar]
  67. Chisholm K.M. Bangs C.D. Bacchi C.E. Kirsch H.M. Cherry A. Natkunam Y. Expression profiles of MYC protein and MYC gene rearrangement in lymphomas. Am. J. Surg. Pathol. 2015 39 3 294 303 10.1097/PAS.0000000000000365 25581730
    [Google Scholar]
  68. Bi C. Huang Y. Ali R. Wang F. Yang X. Bouska A. Xu L. Hao X. Lunning M.A. Chan W.C. Iqbal J. Weisenburger D.D. Vose J.M. Fu K. MYC overexpression in natural killer cell lymphoma: Prognostic and therapeutic implications. Haematologica 2024 109 9 2810 2821 10.3324/haematol.2023.283811 38546691
    [Google Scholar]
  69. Mato S. Castrejón-de-Anta N. Colmenero A. Carità L. Salmerón-Villalobos J. Ramis-Zaldivar J.E. Nadeu F. Garcia N. Wang L. Verdú-Amorós J. Andrés M. Conde N. Celis V. Ortega M.J. Galera A. Astigarraga I. Perez-Alonso V. Quiroga E. Jiang A. Scott D.W. Campo E. Balagué O. Salaverria I. MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma. Blood Cancer J. 2024 14 1 171 10.1038/s41408‑024‑01153‑0 39375391
    [Google Scholar]
  70. de Jonge A.V. Roosma T.J.A. Houtenbos I. Vasmel W.L.E. van de Hem K. de Boer J.P. van Maanen T. Lindauer-van der Werf G. Beeker A. Timmers G.J. Schaar C.G. Soesan M. Poddighe P.J. de Jong D. Chamuleau M.E.D. Diffuse large B-cell lymphoma with MYC gene rearrangements. Eur. J. Cancer 2016 55 140 146 10.1016/j.ejca.2015.12.001 26820684
    [Google Scholar]
  71. Peng Y. Wang Y. Tang N. Sun D. Lan Y. Yu Z. Zhao X. Feng L. Zhang B. Jin L. Yu F. Ma X. Lv C. Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway. J. Exp. Clin. Cancer Res. 2018 37 1 248 10.1186/s13046‑018‑0926‑9 30314513
    [Google Scholar]
  72. Hu J. Xu H. Wu T. Zhang C. Shen H. Dong R. Hu Q. Xiang Q. Chai S. Luo G. Chen X. Huang Y. Zhao X. Peng C. Wu X. Lin B. Zhang Y. Xu Y. Discovery of highly potent and efficient CBP/p300 degraders with strong in vivo antitumor activity. J. Med. Chem. 2024 67 9 6952 6986 10.1021/acs.jmedchem.3c02195 38649304
    [Google Scholar]
  73. Shendy N.A.M. Bikowitz M. Sigua L.H. Zhang Y. Mercier A. Khashana Y. Nance S. Liu Q. Delahunty I.M. Robinson S. Goel V. Rees M.G. Ronan M.A. Wang T. Kocak M. Roth J.A. Wang Y. Freeman B.B. Orr B.A. Abraham B.J. Roussel M.F. Schonbrunn E. Qi J. Durbin A.D. Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition. Nat. Commun. 2024 15 1 3483 10.1038/s41467‑024‑47102‑0 38664416
    [Google Scholar]
  74. Chen Y. Zhao Y. Yao M. Wang Y. Ma M. Yu C. Jiang H. Wei W. Shen J. Xu X. Xie C. Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia. Acta Pharmacol. Sin. 2025 46 5 1390 1403 10.1038/s41401‑025‑01479‑w 39885312
    [Google Scholar]
  75. Liang J. Xu C. Xu J. Yang C. Kong W. Xiao Z. Chen X. Liu Q. Weng Z. Wang J. Jiang G. Jiang Z. Gu A. PPARα senses bisphenol S to trigger ep300-mediated autophagy blockage and hepatic steatosis. Environ. Sci. Technol. 2023 57 51 21581 21592 10.1021/acs.est.3c05010 38085933
    [Google Scholar]
  76. Sacitharan P.K. Gharios G.B. Edwards J.R. Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300: Response to correspondence by Borzì et al. Exp. Mol. Med. 2019 51 3 1 2 10.1038/s12276‑019‑0225‑3 30824682
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206430859250915050817
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The EP300-Targeting Drug CCS1477 Inhibits the Growth and Development ofDiffuse Large B-Cell Lymphoma by Promoting Apoptosis and Mitophagy to Reduce Drug Resistance
Bentham Science Publishers ; https://doi.org/10.2174/0118715206430859250915050817
/content/journals/acamc/10.2174/0118715206430859250915050817
/content/journals/acamc/10.2174/0118715206430859250915050817
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  • Article Type:     Research Article
Keywords: Diffuse large B-cell lymphoma ; apoptosis ; drug resistance ; CCS1477 ; EP300 ; mitophagy

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