Colony stimulating factor-1 (CSF1) is a key cytokine involved in recruitment and activation of tissue macrophages, exerting these effects through binding to a high-affinity receptor tyrosine kinase, the cFMS/CSF1 receptor. Pexidartinib (PLX3397) is a CSF-1R inhibitor that can cross the blood–brain barrier.

In vitro: PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1+ myeloid derived suppressor cells [1].

In vivo: Wild-type C57 mice were orthotopically injected with GL261 cells and fed with PLX3397 compound. After 2 wks, tumors in the control group showed extensive microglia infiltration. In animals fed PLX3397, however, there was a substantial reduction in the number of Iba1- positive cells at the tumor [2].

Clinical trial: In a phase Ib trial, patients with advanced solid tumors are treated with weekly paclitaxel and escalating doses of oral PLX3397 to establish a RP2D of PLX3397. This study will support further development of the PLX3397-paclitaxel combination in the I-SPY-2 neoadjuvant breast cancer trial.