{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:27:12Z","timestamp":1784402832491,"version":"3.55.0"},"reference-count":20,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Cancer Society","award":["RUG 2014-6727"],"award-info":[{"award-number":["RUG 2014-6727"]}]},{"name":"Mandema Stipendium","award":["RUG 2014-6727"],"award-info":[{"award-number":["RUG 2014-6727"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The treatment of young patients with Hodgkin lymphoma (HL) is often successful but a significant proportion of patients suffers from late toxicity. In the current era there are new opportunities for less toxic and more targeted treatment options. In this respect, the anti-apoptotic pathway is an attractive target since Hodgkin tumor cells abundantly express components of this pathway. We measured the effect of BH3 mimetics that interfere with anti-apoptotic proteins in cell lines, also in combination with the standard of care chemotherapeutic doxorubicin and the recently discovered preclinically active tamoxifen. Several anti-apoptotic BCL-2 family proteins were expressed in each case (n = 84) and in HL cell lines (n = 5). Cell lines were checked for sensitivity to BH3 mimetics by BH3 profiling and metabolic assays and monotherapy was only partially successful. Doxorubicin was synergistic with a BCL-XL inhibitor and BCL2\/XL\/W inhibitor navitoclax. Tamoxifen that targets the estrogen receptor \u03b2 present in the mitochondria of the cell lines, could induce cell death, and was synergistic with several BH3 mimetics including\/as well as navitoclax. In conclusion, targeting the anti-apoptotic pathway by the triple inhibitor navitoclax in combination with doxorubicin or tamoxifen is a promising treatment strategy in HL.<\/jats:p>","DOI":"10.3390\/ijms232213751","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:34:52Z","timestamp":1667961292000},"page":"13751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Navitoclax Most Promising BH3 Mimetic for Combination Therapy in Hodgkin Lymphoma"],"prefix":"10.3390","volume":"23","author":[{"given":"Myra","family":"Langendonk","sequence":"first","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nienke A. M.","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Plattel","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9239-1050","authenticated-orcid":false,"given":"Arjan","family":"Diepstra","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-6950","authenticated-orcid":false,"given":"Tom van","family":"Meerten","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-3482","authenticated-orcid":false,"given":"Lydia","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1200\/JCO.2005.04.358","article-title":"Expression of bcl-2 in classical Hodgkin\u2019s lymphoma: An independent predictor of poor outcome","volume":"23","author":"Sup","year":"2005","journal-title":"J. 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