Signaling pathways and potential therapeutic agents in trastuzumab-induced cardiotoxicity

Area of Science:

• Cardiology
• Oncology
• Molecular Biology

Background:

• Trastuzumab (TRZ) is a vital therapy for ErbB2-positive cancers, but its cardiotoxicity (TIC) restricts clinical use.
• TIC stems from ErbB2 signaling blockade, impairing cardiomyocyte repair and antioxidant capacity, leading to oxidative stress and cell death pathways.
• Key signaling pathways like PI3K/Akt, MAPK, and NLRP3 are implicated in TIC.

Purpose of the Study:

• To consolidate current knowledge on Trastuzumab-induced cardiotoxicity (TIC).
• To elucidate the molecular mechanisms underlying TIC.
• To provide insights for developing novel cardioprotective strategies against TIC.

Main Methods:

• Comprehensive literature review of studies investigating Trastuzumab-induced cardiotoxicity.
• Analysis of molecular pathways and cellular events involved in TIC.
• Exploration of potential therapeutic targets and agents for cardioprotection.

Main Results:

• Decades of research have identified multiple signaling pathways (e.g., PI3K/Akt, MAPK, NLRP3) involved in TIC.
• Mechanisms include compromised cardiomyocyte repair, oxidative stress, apoptosis, ferroptosis, and pyroptosis.
• Various potential therapeutic agents targeting key molecules in TIC have been explored.

Conclusions:

• A comprehensive understanding of TIC mechanisms is crucial for clinical application.
• Targeting specific molecular pathways offers promise for novel cardioprotective strategies.
• Further research is needed to translate these findings into effective clinical interventions for TIC.