The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review.
Dareuosh ShackebaeiMahvash HesariSara GorganiZeinab VafaeipourSanaz SalaramoliFatemeh YarmohammadiPublished in: Cell biochemistry and biophysics (2024)
Doxorubicin (DOX) is a chemotherapy drug known to induce metabolic changes in the heart, leading to potential heart toxicity. These changes impact various cellular functions and pathways such as disrupting the mechanistic target of rapamycin (mTOR) signaling pathway. The study aimed to investigate the effect of DOX on the mTOR pathway through an in vivo systematic review. Databases were searched on September 11, 2023. We finally included 30 in vivo studies that examined the mTOR expression in cardiac tissue samples. The present study has shown that the PI3K/AKT/mTOR, the AMPK/mTOR, the p53/mTOR signaling, the mTOR/TFEB pathway, the p38 MAPK/mTOR, the sestrins/mTOR, and the KLF15/eNOS/mTORC1 signaling pathways play a crucial role in the development of DOX-induced cardiotoxicity. Inhibition or dysregulation of these pathways can lead to increased oxidative stress, apoptosis, and other adverse effects on the heart. Strategies that target and modulate the mTOR pathways, such as the use of mTOR inhibitors like rapamycin, have the potential to enhance the anticancer effects of DOX while also mitigating its cardiotoxic side effects.
Keyphrases
- cell proliferation
- oxidative stress
- signaling pathway
- systematic review
- heart failure
- diabetic rats
- poor prognosis
- squamous cell carcinoma
- nitric oxide
- machine learning
- epithelial mesenchymal transition
- long non coding rna
- dna damage
- induced apoptosis
- cell death
- deep learning
- ischemia reperfusion injury
- endothelial cells
- cancer therapy
- big data
- high glucose
- adverse drug
- rectal cancer
- oxide nanoparticles