Repurposing Carfilzomib as a Promising Drug for Targeted Therapy in Gastric Cancer

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Gastric cancer (GC) research is actively seeking novel therapeutic targets.
• The gene Psmb8 (proteasome subunit beta type 8), encoding an immunoproteasome subunit, is upregulated in GC and linked to disease severity.
• Elevated PSMB8 expression is observed in gastric cancer patient samples.

Purpose of the Study:

• To investigate PSMB8 as a potential therapeutic target for gastric cancer.
• To evaluate the efficacy of carfilzomib, a PSMB8-targeting drug, in preclinical gastric cancer models.

Main Methods:

• Utilized a Helicobacter-induced gastric cancer mouse model to identify differentially expressed genes, including Psmb8.
• Screened public databases to identify carfilzomib as a potential drug targeting PSMB8.
• Assessed carfilzomib's efficacy alone and in combination with 5-fluorouracil (5-FU) in human gastric tumor xenografts in nude mice, measuring tumor growth, proliferation, and apoptosis.

Main Results:

• Carfilzomib treatment significantly retarded tumor growth in gastric cancer models.
• The drug effectively inhibited cancer cell proliferation.
• Carfilzomib induced significant apoptosis in tumor cells.

Conclusions:

• PSMB8 is a viable target for novel gastric cancer therapies.
• Carfilzomib demonstrates potent anti-tumor activity and warrants further investigation as a treatment option for cancers with high PSMB8 expression.