Emerging agents that target signaling pathways in cancer fibroblast cells (Review)

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Cancer-associated fibroblasts (CAFs) are key drivers of tumor development, recurrence, and metastasis.
• Multiple signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, and TGF-β, regulate CAF functions.
• Targeting specific pathways, such as ferroptosis, offers a direct approach to eliminate CAFs.

Purpose of the Study:

• To review current research on small molecule compounds that inhibit CAF progression.
• To highlight the role of various signaling pathways in CAF development and function.
• To explore novel therapeutic strategies targeting CAFs in cancer treatment.

Main Methods:

• Review of existing literature on small molecule inhibitors and activators of CAF-related pathways.
• Analysis of signaling pathways including PI3K/AKT/mTOR, JAK/STAT, TGF-β, NF-κB, FAP, ferroptosis, apoptosis, and autophagy.
• Evaluation of the druggability and pharmacokinetic profiles of small molecule compounds.

Main Results:

• Small molecule drugs targeting PI3K/AKT/mTOR, JAK/STAT, TGF-β, and NF-κB pathways can inhibit CAF progression.
• Activators of FAP, ferroptosis, apoptosis, and autophagy pathways demonstrate potential in targeting CAFs.
• Small molecules possess favorable druggability and pharmacokinetic properties for cancer therapy.

Conclusions:

• Targeting CAFs via small molecule inhibitors or activators of key signaling pathways presents a promising therapeutic strategy.
• These compounds underscore the critical role of CAFs in tumor progression.
• Further clinical investigation of small molecule-based CAF-targeting therapies is warranted.