Cancer-associated fibroblasts in non-small cell lung cancer therapy: Challenges and opportunities

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment Research

Background:

• Non-small cell lung cancer (NSCLC) presents significant morbidity and mortality challenges.
• The tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), plays a critical role in NSCLC progression and treatment resistance.
• Current therapeutic strategies for NSCLC often yield limited benefits due to TME complexities.

Purpose of the Study:

• To review the diverse subsets of CAFs within the NSCLC TME.
• To elucidate the mechanisms by which CAFs influence the efficacy of various NSCLC treatments, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy.
• To synthesize the translational progress and identify limitations and future opportunities for CAF-targeted strategies in NSCLC.

Main Methods:

• Comprehensive literature review of studies on CAFs in NSCLC.
• Analysis of CAF heterogeneity, origin, function, and plasticity.
• Examination of CAF interactions with different therapeutic modalities.
• Synthesis of translational data on CAF-targeted therapies.

Main Results:

• CAFs exhibit significant heterogeneity in origin, definition, and function within NSCLC.
• CAF plasticity complicates the development of effective targeted therapies.
• Some CAF-targeting interventions have shown paradoxical effects, including accelerated disease progression.
• CAFs critically influence the response to chemotherapy, radiotherapy, immunotherapy, and targeted therapy in NSCLC.

Conclusions:

• Targeting CAFs in NSCLC presents a promising therapeutic avenue, but challenges related to heterogeneity and plasticity must be addressed.
• A deeper understanding of specific CAF subsets and their roles is essential for designing effective and safe therapeutic strategies.
• Future research should focus on overcoming current limitations to advance the clinical translation of CAF-targeted therapies for improved NSCLC patient outcomes.