The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review

Area of Science:

• Cardiology
• Oncology
• Molecular Biology

Background:

• Doxorubicin (DOX) is a vital chemotherapy agent with known cardiotoxic side effects.
• DOX-induced cardiotoxicity is linked to metabolic and signaling pathway disruptions in the heart.
• The mechanistic target of rapamycin (mTOR) pathway is implicated in cellular stress responses and drug toxicity.

Purpose of the Study:

• To systematically review in vivo studies investigating the role of the mTOR signaling pathway in Doxorubicin-induced cardiotoxicity.
• To identify specific mTOR-related pathways affected by DOX treatment in cardiac tissues.
• To explore potential therapeutic strategies targeting mTOR to mitigate DOX cardiotoxicity.

Main Methods:

• Systematic review of in vivo studies.
• Searched databases for studies examining mTOR expression in cardiac tissue after DOX administration.
• Included 30 relevant studies in the final analysis.

Main Results:

• DOX significantly impacts multiple mTOR-related signaling pathways, including PI3K/AKT/mTOR, AMPK/mTOR, p53/mTOR, mTOR/TFEB, p38 MAPK/mTOR, sestrins/mTOR, and KLF15/eNOS/mTORC1.
• Dysregulation of these pathways contributes to oxidative stress, apoptosis, and overall cardiotoxicity.
• These pathways are crucial in the development and progression of DOX-induced heart damage.

Conclusions:

• The mTOR signaling network is central to Doxorubicin-induced cardiotoxicity.
• Targeting and modulating specific mTOR pathways, for instance, using mTOR inhibitors like rapamycin, presents a promising strategy.
• Such interventions could potentially enhance DOX efficacy against cancer while simultaneously reducing its detrimental effects on the heart.