Doxorubicin : an overview of the anti-cancer and chemoresistance mechanisms

Abstract

Cancer remains one of the highest leading causes of morbidity and mortality worldwide. Anthracyclines, specifically Doxorubicin (DOX), have been used for the past three decades as a treatment against a number of cancers. However, its use has been limited due to its severe side effects and toxicity arising during or after treatment. Ample research has already taken place and is still being undertaken in order to understand the mode of action of anthracyclines, including DOX. However, despite the work carried out; the mechanisms proposed remain controversial. Other research has also taken place to get a better understanding of the cell death and growth arrest pathways triggered by DOX. Even though DOX remains one of the most effective chemotherapeutic drugs, resistance development in cancer cells remains a major barrier to effective treatment when using this drug. Apart from the already known mechanisms of DOX chemoresistance, research has shown that post-translational modifications on certain proteins can also contribute to DOX chemoresistance. However, the mechanisms by which DOX resistance arises remain poorly defined. This review tackles some of the currently understood and proposed models for the mode of action of DOX, including the cell death mechanisms triggered by DOX and the DOX resistance mechanisms arising during treatment. By further understanding how DOX functions, its influence on cell biological events and the mechanisms contributing to DOX resistance; it can further help in improving the efficiency and efficacy of the drug, together with decreasing its toxicity.