Tumour associated macrophages (TAMs) support several key aspects of tumour progression that include angiogenesis, immune suppression, invasion and metastasis. Tumours containing large numbers of TAMs, such as breast cancer, are highly metastatic and are likely to be susceptible to TAM targeting therapies. However, reprogramming TAMs from pro-tumoural into anti-tumoural cells may be a more effective approach than total macrophage ablation.
We have previously shown that the growth factor CSF-1 controls macrophage motility and invasion via PI3K p110δ and the Src family kinase, Hck, in vitro. Our recent preclinical studies in a mouse model of breast cancer have shown striking reductions in tumour growth of 50% and 80% with selective inhibition of either PI3K p110δ (GS9820) or Hck (RK-20449) respectively. Subsequent single cell RNAseq analysis of RK-20449 treated mammary tumours demonstrates that Hck inhibition re-educates TAMs towards an anti-tumoural phenotype. We propose that this novel effect on TAMs by RK-20449 is a key factor in its ability to significantly affect tumour progression.