Investigational platelet-derived growth factor receptor kinase inhibitors in breast cancer therapy

Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical evidence further suggests tumor stimulatory roles of PDGFRs expressed by tumor stroma cells and indicates a deleterious effect of stromal PDGFRs on intratumoral drug uptake.

This review summarizes the present understanding of PDGF signaling in breast cancer based on experimental studies and available clinical trials. It also provides a critical discussion of selected ongoing clinical trials in patients with breast cancer involving PDGFR inhibition with tyrosine kinase inhibitors, specifically in endocrine responsive breast cancer.

An increased molecular understanding of response and resistance mechanisms to endocrine therapy will be essential for therapeutic advances in PDGFR-directed cancer therapy. Future developments in the field will rely on clinical studies where prospective analyses of target expression in breast cancer cells and in the tumor stroma are included. More selective PDGFR inhibitors with reduced side effects will be crucial for combinatorial therapies. Development of sensitive diagnostics is of critical importance for patient selection and monitoring of therapeutic effects.