Targeting RIPK1 to modulate cell death and tumour microenvironment in cancer therapy

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) plays a critical role in regulating inflammation, apoptosis, and necroptosis.
• RIPK1 is implicated in various human diseases, including cancer, neurodegenerative disorders, and autoimmune diseases.
• In cancer, RIPK1 activity promotes an immunosuppressive tumor microenvironment, immune evasion, metastasis, and therapeutic resistance, contributing to an immunologically cold phenotype.

Purpose of the Study:

• To review the biological functions of RIPK1.
• To elaborate on RIPK1's roles in cancer progression, focusing on the tumor immune microenvironment, metastasis, and chemoresistance.
• To identify RIPK1-targeted inhibitors for potential cancer therapy.

Main Methods:

• Literature review and synthesis of existing research on RIPK1.
• Analysis of RIPK1's involvement in cancer hallmarks.
• Compilation of identified RIPK1 inhibitors and their therapeutic potential.

Main Results:

• RIPK1 suppresses immunogenic cell death and fosters an immunosuppressive tumor microenvironment.
• Targeting RIPK1 can potentially overcome resistance to immune checkpoint blockade and convert tumors to an immunologically hot phenotype.
• Several RIPK1 inhibitors show promise for cancer treatment.

Conclusions:

• RIPK1 is a significant therapeutic target in oncology.
• Targeting RIPK1 offers a strategy to enhance anti-tumor immunity and combat therapeutic resistance.
• Further research is needed to fully explore the therapeutic opportunities and challenges associated with RIPK1 inhibition in cancer.