Cancer treatment-induced cardiotoxicity: a cardiac stem cell disease?
Cardiovascular diseases and cancer represent respectively the first and second cause of death in industrialized countries. These two conditions may become synergistic when cardiovascular complications of anti-cancer therapy are considered. More than 70% of childhood and 50% of adult cancer patients can be cured, however this important success obtained by the biological and medical research is obfuscated by emerging findings of early and late morbidity due to cardiovascular events. Although anthracyclines are effective drugs against cancer a dose-dependent cardiotoxic effects whose mechanism has not been elucidated resulting in failure of therapeutic interventions limit their use. Unexpectedly, tyrosine/kinase inhibitors (TKIs) aimed at molecularly interfering with oncogenic pathways, have been implicated in cardiac side effects. Possible explanations of this phenomenon have been ambiguous, further strengthening the need to deepen our understanding on the mechanism of cardiotoxicity. In addition to a detailed description of anthracyclines and TKIs-related cardiovascular effects, the present review highlights recent observations supporting the hypothesis that the cellular target of anthracyclines and TKIs may include myocardial compartments other than parenchymal cells. The demonstration that the adult mammalian heart possesses a cell turnover regulated by primitive cells suggests that this cell population may be implicated in the onset and development of cardiovascular effects of anti-cancer strategies. The possibility of preventing cardiotoxicity by preservation and/or expansion of the resident stem cell pool responsible for cardiac repair may open new therapeutic options to unravel an unsolved clinical issue.
Prezioso
Lucia
L
Department of Medicine, University of Parma, Via Gramsci 14, Parma, Italy.
Tanzi
Silvia
S
Galaverna
Federica
F
Frati
Caterina
C
Testa
Beatrice
B
Savi
Monia
M
Graiani
Gallia
G
Lagrasta
Costanza
C
Cavalli
Stefano
S
Galati
Serena
S
Madeddu
Denise
D
Lodi Rizzini
Elisa
E
Ferraro
Francesca
F
Musso
Ezio
E
Stilli
Donatella
D
Urbanek
Konrad
K
Piegari
Elena
E
De Angelis
Antonella
A
Maseri
Attilio
A
Rossi
Francesco
F
Quaini
Eugenio
E
Quaini
Federico
F
D000818:Animals; D018943:Anthracyclines / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D054715:Cardiotoxins / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013234:Stem Cells / Q000187:drug effects
D018943:Anthracyclines; D000970:Antineoplastic Agents; D054715:Cardiotoxins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases