Antitumor therapy with doxorubicin and other anthracyclines is limited by the possible development of cardiomyopathy upon chronic administration. Several lines of evidence suggest that a close link exists between cardiotoxicity and the amount of anthracycline that accumulates in the heart and then undergoes one- or two- electron reduction to toxic metabolites or by-products. Alternative metabolic pathways lead to an oxidative degradation of anthracyclines, possibly counteracting anthracycline accumulation and reductive bioactivation; unfortunately, however, the actual role of anthracycline oxidation is only partially characterized. Here, we briefly review the biochemical foundations of reductive versus oxidative anthracycline metabolism. We show that multiple links exist between one pathway of toxic biactivation and another, limiting the search and clinical development of "better anthracyclines" that retain antitumor activity but induce less cardiotoxicity than the available analogues.

An introduction to the metabolic determinants of anthracycline cardiotoxicity / P. Menna, S. Recalcati, G. Cairo, G. Minotti. - In: CARDIOVASCULAR TOXICOLOGY. - ISSN 1530-7905. - 7:2(2007), pp. 80-85.

An introduction to the metabolic determinants of anthracycline cardiotoxicity

S. Recalcati
Secondo
;
G. Cairo
Penultimo
;
2007

Abstract

Antitumor therapy with doxorubicin and other anthracyclines is limited by the possible development of cardiomyopathy upon chronic administration. Several lines of evidence suggest that a close link exists between cardiotoxicity and the amount of anthracycline that accumulates in the heart and then undergoes one- or two- electron reduction to toxic metabolites or by-products. Alternative metabolic pathways lead to an oxidative degradation of anthracyclines, possibly counteracting anthracycline accumulation and reductive bioactivation; unfortunately, however, the actual role of anthracycline oxidation is only partially characterized. Here, we briefly review the biochemical foundations of reductive versus oxidative anthracycline metabolism. We show that multiple links exist between one pathway of toxic biactivation and another, limiting the search and clinical development of "better anthracyclines" that retain antitumor activity but induce less cardiotoxicity than the available analogues.
Settore MED/04 - Patologia Generale
2007
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/45904
Citazioni
  • ???jsp.display-item.citation.pmc??? 21
  • Scopus 65
  • ???jsp.display-item.citation.isi??? 61
social impact