Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer.

Introduction: Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment, being implicated in enhancing tumor growth and fostering drug resistance. Nonetheless, the mechanisms underlying their function in prostate cancer (PCa) remain incompletely understood, which is essential for devising effective therapeutic strategies.

Objectives: The main objective of this study was to explore the mechanisms by which CAFs mediate PCa growth and chemoresistance.

Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis.

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape.