Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients.

Autor: Qiao X; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. x.qiao@nki.nl.; Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands. x.qiao@nki.nl., van der Zanden SY; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands., Li X; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China., Tan M; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands., Zhang Y; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China., Song JY; Division of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van Gelder MA; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands., Hamoen FL; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands., Janssen L; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands., Zuur CL; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Pang B; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands., van Tellingen O; Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Li J; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. drlijunmin@126.com.; Wuxi Branch of Ruijin Hospital, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai , 200025, China. drlijunmin@126.com., Neefjes J; Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, Leiden, The Netherlands. j.j.c.neefjes@lumc.nl.
Jazyk: angličtina
Zdroj: Molecular cancer [Mol Cancer] 2024 Jun 04; Vol. 23 (1), pp. 120. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1186/s12943-024-02034-7
Abstrakt: The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
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