A comprehensive review on time-tested anticancer drug doxorubicin

Doxorubicin or Adriamycin, is one of the most widely used chemotherapeutic drug for treating a myriad of cancers. It induces cell death through multiple intracellular targets: reactive oxygen species generation, DNA-adduct formation, topoisomerase II inhibition, histone eviction, Ca²⁺ and iron hemostasis regulation, and ceramide overproduction. Moreover, doxorubicin-treated dying cells undergo cellular modifications that enable neighboring dendritic cell activation and enhanced presentation of tumor antigen. In addition, doxorubicin also aids in the immune-mediated clearance of tumor cells. However, the development of chemoresistance and cardiotoxicity side effect has undermined its widespread applicability. Several formulations of doxorubicin and co-treatments with inhibitors, miRNAs, natural compounds and other chemotherapeutic drugs have been essential in reducing its dosage-dependent toxicity and combating the development of resistance. Further, more advanced research into the molecular mechanism of chemoresistance development would be vital in improving the overall survivability of clinical patients and in preventing cancer relapse.