Clinical utilities of platelet-derived growth factor signaling in breast cancer.

Platelet-derived growth factors (PDGFs) and their cognate receptors (PDGFRα/β) play critical roles in breast cancer progression and metastasis. This review summarizes current evidence of PDGF ligand and receptor expression patterns, oncogenic functions, prognostic significance and therapeutic targetability, with a specific focus on small molecule inhibition. PDGF-PDGFR signaling is known to contribute to epithelial to mesenchymal transition, cancer stem cell maintenance, desmoplasia, angiogenesis, and immune modulation. Additionally, the four PDGF ligands have distinct oncogenic functions. PDGFA and PDGFB have been implicated in breast cancer associated brain metastasis, while PDGFC has been shown to play a crucial role in fibroblast activation. PDGFD, while less studied, may activate epithelial to mesenchymal transition in breast cancer. High expression of PDGFA, PDGFB, PDGFC, and stromal PDGFRβ correlate with poor patient survival, highlighting their potential as candidate biomarkers. We specifically focus on evaluating current therapeutic strategies which target the PDGF-PDGFR axis, including neutralizing antibodies, aptamers, and small molecule inhibitors, which show preclinical promise but limited clinical success in breast cancer to date. We discuss future research directions with emphasis on identifying selective inhibitors, utilizing PDGF-PDGFR signaling components for patient stratification, and combination with immunotherapies.