Emerging agents that target signaling pathways in cancer fibroblast cells (Review).
- 2026-06-03
- International journal of oncology 69(1)
- Yan Wan
- Xiang-Qing Liu
- Dong Liu
- Ke-Di Li
- Dan-Dan Zhang
- PubMed: 42246174
- DOI: 10.3892/ijo.2026.5900
Study Design
- Type
- Review
- Funding
- Unclear
Cancer‑associated fibroblasts (CAFs) play a critical role in cancer development, recurrence and metastasis. Several signaling pathways are crucial in CAF development, including fibroblast activation protein (FAP), phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), Janus kinase/signal transducers and activators of transcription (JAK/STAT), nuclear factor κB (NF‑κB), transforming growth factor β (TGF‑β), ferroptosis, apoptosis and autophagy pathways. Targeting the ferroptosis signaling pathway specifically kills CAFs. Therefore, targeting these pathways may inhibit the protumorigenic functions of CAFs. Small molecule drugs, due to their well‑dispersed spatial structures and distinct chemical properties, exhibit promising druggability and pharmacokinetic profiles. These characteristics make small molecule drugs highly advantageous in drug development and increasingly favored in the market. The present review summarized current studies on small molecule compounds that inhibit CAF progression, encompassing inhibitors of the PI3K/AKT/mTOR, JAK/STAT, TGF‑β and NF‑κB pathways, as well as activators of the FAP, ferroptosis, apoptosis and autophagy pathways. These small molecule compounds underscore the significance of CAFs in tumor progression and suggest novel strategies for cancer treatment by targeting CAFs in clinical settings.