Fig 1.

Proposed mechanism of the activation of NLRP3 inflammasome following the administration of cancer therapies. Cancer treatment induces cardiomyocyte injury, which mediates the priming signaling of the NLRP3 inflammasome. NF-KB is activated, migrates to the nucleus, and begins the synthesis of the inactive NLRP3 components. Mitochondrial dysfunction in the heart consequently results in oxidative stress. Coupled with impaired autophagy, this then leads to the triggering of the NLRP3. The NLRP3 then oligomerizes and induces an auto-proteolytical activation of caspase-1. Active caspase-1 processes pro-IL1β and pro-IL18 into their mature forms, and triggers pyroptotic myocardial cell death. This NLRP3-mediated cardiac injury can induce long-term consequences on the heart, leading to the onset of heart failure.