release, collectively establishing a positive feedback loop disrupting calcium homeostasis. Mechanistically, calcium overload induces mitochondrial membrane potential dissipation and sustained mPTP opening, triggering mitochondrial oxidative stress and energy metabolic disorders. This mitochondrial crisis concurrently activates caspase-3, GSDMD, and RIPK1, synergistically initiating apoptosis, pyroptosis, and necroptosis, ultimately converging into PANoptosis with potent immunostimulatory potential. This strategy, encompassing targeted accumulation, calcium storm activation, and multi-modal cell death synergy, provides a biologically precise approach to overcoming immunotherapy resistance in CRC.
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Yu-Ying Xiao
Yuxuan Yang
Haosen Qiu
Advanced Science
Southern Medical University
Guangzhou Medical University
Nanfang Hospital
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Xiao et al. (Wed,) studied this question.
www.synapsesocial.com/papers/69fd7e5cbfa21ec5bbf0699d — DOI: https://doi.org/10.1002/advs.75559