PANoptosis in hepatocellular carcinoma: Underlying mechanisms

Table 1 PANoptosis and cancer therapeutic strategies

Potential therapeutic strategy	Name	Effect	Mechanism	Ref.
Traditional laboratory therapy	TNF-α/IFN-γ	-	Triggers a PANoptosis cascade, exhibiting anti-tumor activity	[44]
		+	May promote immune escape by inhibiting T-cell function	-
	KLX	-	Induces PANoptosis by altering ZBP1 conformation.	[26]
	PPDPF	-	Regulates TRIM21 to ubiquitinate RIPK1, further inhibiting HCC progression	[78]
	OTULIN	-	Inhibits FADD/RIPK1-mediated hepatocyte apoptosis, protecting liver cells and preventing liver inflammation and HCC	[77]
	DNASE1 L3	-	Activates the AIM2 pathway, thereby inducing PANoptosis	[35]
	HMOX1	+	Silencing reduces HCC resistance to sorafenib	[92]
	Fn-OMV/oHSV	-	Combined use enhances inflammatory responses and improves immune checkpoint blockade (ICB) efficacy	[93]
	ADAR1	+	Blocking ADAR1 activates ZBP1-mediated PANoptosis, inhibiting tumorigenesis	[94]
Novel nanotherapies	Bi2Sn2O7	-	Through ultrasound-responsive catalytic effects, generates enhanced enzyme kinetic effects for HCC treatment and inhibition of later-stage lung metastasis; also targets mitochondrial disruption, disrupting energy metabolism and amplifying ROS levels	[95]
	Fullerenols	-	Affects mitochondrial function and induces endoplasmic reticulum stress	[96]

ADAR1: Adenosine deaminase, RNA-specific 1; AIM2: Absent in melanoma 2; Bi2Sn2O7: Bismuth tin oxide; DNASE1 L3: Deoxyribonuclease 1 class 3; FADD: Fas-associated protein with death domain; Fn-OMV: Fusobacterium nucleatum outer membrane vesicle; HCC: Hepatocellular carcinoma; HMOX1: Heme oxygenase 1; ICB: Immune checkpoint blockade; IFN-γ: Interferon-gamma; KLX: Kanglexin; oHSVs: Human alphaherpesvirus 1-based oncolytic viruses; OS: Oxidative stress; OTULIN: OTU deubiquitinase with linear linkage specificity; PPDPF: Pancreatic progenitor cell differentiation and proliferation factor; RIPK1: Receptor-interacting serine/threonine kinase 1; TNF-α: Tumor necrosis factor-alpha; TRIM21: Tripartite motif containing 21; ZBP1: Z-DNA binding protein 1.