Doxorubicin-induced death in tumour cells and cardiomyocytes: is autophagy the key to improving future clinical outcomes?

Abstract

Abstract Objectives Doxorubicin, a commonly used frontline chemotherapeutic agent for cancer, is not without side-effects. The original thinking that the drug causes necrosis in tumours has largely given way to its link with apoptosis over the past two decades. Key findings More recently, major biomarkers such as AMPK, p53 and Bcl-2 have been identified as important to apoptosis induction by doxorubicin. It is Bcl-2 and its interaction with Beclin-1 that has refocussed research attention on doxorubicin, albeit this time for its ability to induce autophagy. Autophagy can be either anticancerous or procancerous however, so it is critical that the reasons for which cancer cells undergo this type of cell biological event be clearly identified for future exploitation. Summary Taking a step back from treating patients with large doses of doxorubicin, which causes toxicity to the heart amongst other organs, and further research with this drug's molecular signalling in not only neoplastic but normal cells, may indeed redefine the way doxorubicin is used clinically and potentially lead to better neoplastic disease management.