mTOR: good, bad, or ugly?

This editorial refers to ‘Inhibition of AMPK signalling by doxorubicin: at the crossroads of the cardiac responses to energetic, oxidative, and genotoxic stress’ by S. Gratia et al ., pp. 290–299, this issue. Doxorubicin (DXR) is one of the most widely used chemotherapeutics in the treatment of a variety of cancers, including breast, prostate, stomach and liver tumours, soft tissue sarcomas, leukaemias, and lymphomas.1 The anti-malignancy effects of DXR are attributed to its interaction with the DNA helix and proteins involved in DNA replication and transcription, resulting in the inhibition of synthesis of DNA, RNA, and proteins and ultimately cell death.2 However, DXR causes severe cardiomyopathy and resultant congestive heart failure, especially in patients treated with a high dose or in high-risk populations such as children, adolescents, or patients with predisposed cardiac problems. DXR-induced cardiac injury is manifested as acute or chronic cardiomyopathy, and both can eventually develop into severe congestive heart failure.Over the past few decades, extensive studies have been focused on the mechanisms underlying DXR-induced cardiotoxicity. Although multiple mechanisms have been implicated, oxidative stress-mediated death of cardiac myocytes has been identified as one of the most important. It is now well established that DXR-induced cardiomyopathy is associated with myocyte energetic stress, oxidative …