CRISPR/Cas9 gene editing in gastric cancer: Mechanisms, advances, and therapeutic potential

Table 1 Overview of clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 applications in gastric cancer: Gene targets, delivery strategies, and clinical relevance

Gene target	Function	Delivery strategy	Preclinical/clinical relevance	Ref.
TP53	Tumor suppressor gene regulating cell cycle and apoptosis	Lentiviral vector, lipid nanoparticles	Restoration of p53 function suppresses tumor growth in GC models	[62,63]
CDH1	Encodes E-cadherin; involved in cell adhesion and EMT	CRISPR/Cas9 ribonucleoprotein complexes	CDH1 knockout mimics hereditary diffuse gastric cancer; used in disease modeling	[64,65]
KRAS	Oncogene involved in MAPK signaling pathway	AAV vectors	Editing KRAS mutations reduces cell proliferation and tumorigenesis	[66]
PIK3CA	Encodes PI3K catalytic subunit; promotes growth signaling	Liposomal CRISPR delivery	Disruption impairs PI3K/AKT signaling, reducing tumor progression	[67]
HER2 (ERBB2)	Oncogene, overexpressed in about 15%-20% of GC cases	Nanoparticle-based CRISPR delivery	Knockout increases response to chemotherapy in HER2 + GC models	[30]
MET	Proto-oncogene encoding hepatocyte growth factor receptor	Electroporation-based plasmid delivery	Targeting MET suppresses invasion and metastasis in GC cells	[68]
PD-L1 (CD274)	Immune checkpoint protein; mediates immune evasion	Dual CRISPR-Cas9/anti-PD-L1 delivery systems	Enhances antitumor immunity, improves immunotherapy response	[68]

CRISPR: Clustered regularly interspaced short palindromic repeats; Cas9: Clustered regularly interspaced short palindromic repeats-associated protein 9; RNP: Ribonucleoprotein; AAV: Adeno-associated virus; EMT: Epithelial-mesenchymal transition; CDH1: Cadherin 1; MAPK: Mitogen-activated protein kinase; KRAS: Kirsten rat sarcoma viral oncogene homolog; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; GC: Gastric cancer; HER2: Human epidermal growth factor receptor 2; MET: Mesenchymal-epithelial transition factor; PD-L1: Programmed death-ligand 1.