TY - JOUR
T1 - Anthracycline-induced cardiotoxicity — are we about to clear this hurdle?
AU - Dempke, Wolfram C.M.
AU - Zielinski, Rafal
AU - Winkler, Christina
AU - Silberman, Sandra
AU - Reuther, Susanne
AU - Priebe, Waldemar
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/5
Y1 - 2023/5
N2 - Anthracyclines have contributed significantly to remarkable improvements in overall survival and are regarded as the most effective cytostatic drug for cancer treatment in various malignancies. However, anthracyclines are a significant cause of acute and chronic cardiotoxicity in cancer patients, and long-term cardiotoxicity can lead to death in about one-third of patients. Several molecular pathways have been implicated in the development of anthracycline-induced cardiotoxicity, although the underlying mechanisms of some molecular pathways are not fully elucidated. It is now generally believed that anthracycline-induced reactive oxygen species (resulting from intracellular metabolism of anthracyclines) and drug-induced inhibition of topoisomerase II beta are the key mechanisms responsible for the cardiotoxicity. To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.
AB - Anthracyclines have contributed significantly to remarkable improvements in overall survival and are regarded as the most effective cytostatic drug for cancer treatment in various malignancies. However, anthracyclines are a significant cause of acute and chronic cardiotoxicity in cancer patients, and long-term cardiotoxicity can lead to death in about one-third of patients. Several molecular pathways have been implicated in the development of anthracycline-induced cardiotoxicity, although the underlying mechanisms of some molecular pathways are not fully elucidated. It is now generally believed that anthracycline-induced reactive oxygen species (resulting from intracellular metabolism of anthracyclines) and drug-induced inhibition of topoisomerase II beta are the key mechanisms responsible for the cardiotoxicity. To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.
KW - Anthracyclines
KW - Cardiotoxicity
KW - Clinical trials
KW - Doxorubicin analogues
UR - http://www.scopus.com/inward/record.url?scp=85150888967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85150888967&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2023.02.019
DO - 10.1016/j.ejca.2023.02.019
M3 - Article
C2 - 36966697
AN - SCOPUS:85150888967
SN - 0959-8049
VL - 185
SP - 94
EP - 104
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -