ZSH-2208: A novel retinoid with potent anti-tumour effects on ESCC stem cells via RARγ-TNFAIP3 axis

Area of Science:

• Oncology
• Drug Discovery
• Molecular Biology

Background:

• Oesophageal cancer, particularly oesophageal squamous cell carcinoma (ESCC), is a global health concern.
• Cancer stem cells (CSCs) drive ESCC progression, leading to recurrence and drug resistance.
• Existing treatments lack effective strategies targeting ESCC CSCs.

Purpose of the Study:

• To develop novel retinoids targeting ESCC CSCs.
• To identify a potent and safe therapeutic candidate for ESCC.
• To elucidate the mechanism of action for targeting ESCC TRCs.

Main Methods:

• Development and optimization of novel retinoids targeting retinoic acid receptors (RARs).
• Pharmacological validation and mechanistic studies of ZSH-2208.
• In vitro and in vivo experiments to assess efficacy against ESCC-TRCs.

Main Results:

• ZSH-2208, a novel retinoid, was identified as a promising agent against ESCC-TRCs.
• ZSH-2208 effectively inhibits ESCC-TRC growth through the RARγ-TNFAIP3 axis.
• The study demonstrated the clinical significance of TNFAIP3 in ESCC.

Conclusions:

• ZSH-2208 effectively inhibits ESCC-TRCs, which share characteristics with ESCC stem cells.
• The RARγ-TNFAIP3 pathway is a key target for ZSH-2208 in ESCC.
• Lower TNFAIP3 protein levels may correlate with better survival in ESCC patients.