A comprehensive review on time-tested anticancer drug doxorubicin

Area of Science:

• Oncology
• Pharmacology
• Immunology

Background:

• Doxorubicin (Adriamycin) is a cornerstone chemotherapy agent for diverse cancers.
• It functions through multiple intracellular pathways, including DNA damage, enzyme inhibition, and oxidative stress.
• Doxorubicin also modulates the immune system to aid tumor antigen presentation and clearance.

Purpose of the Study:

• To review the multifaceted mechanisms of doxorubicin-induced cell death and anti-tumor immunity.
• To discuss the significant challenges of chemoresistance and cardiotoxicity associated with doxorubicin therapy.
• To highlight strategies for mitigating doxorubicin's toxicity and overcoming resistance.

Main Methods:

• Literature review of doxorubicin's molecular targets and cellular effects.
• Analysis of mechanisms underlying chemoresistance and cardiotoxicity.
• Examination of therapeutic strategies including novel formulations and co-treatments.

Main Results:

• Doxorubicin induces cancer cell death via DNA damage, topoisomerase II inhibition, ROS generation, and immune system modulation.
• Dying cells treated with doxorubicin enhance dendritic cell activation and tumor antigen presentation.
• Chemoresistance and cardiotoxicity are major dose-limiting toxicities that hinder doxorubicin's clinical application.

Conclusions:

• Doxorubicin's efficacy is linked to its diverse cytotoxic and immunomodulatory actions.
• Strategies like advanced formulations and combination therapies are crucial for reducing toxicity and combating resistance.
• Further research into chemoresistance mechanisms is essential for improving patient outcomes and preventing cancer recurrence.