Hck activation

The cellular composition of the tumour microenvironment affects how well a tumour can grow and respond to targeted and immune-modulatory therapy. Although these processes are affected by many different cell types within the tumour stroma, macrophages and other myeloid-derived cells are among the most important players. We have found that the myeloid cell kinase Hck is highly abundant in the tumour microenvironment and aberrant Hck activation suppresses an effective anti-tumour immune response. We continue to validate, in complementary models for solid tumours, the beneficial role resulting from the inhibition of the HCK kinase as a means to confer increased anti-tumour responses elicited by immunecheckpoint blockade. In parallel, our Lab, in collaboration with industry partners, is making progress towards the development of HCK-specific drug-like inhibitors.

Stat3 and tumourigenesis

Pronounced epithelial Stat3 activity is not only observed during wound-healing, but also in a majority of cancers including those in the colon, stomach, breast and lung. Our lab recently established a novel link, showing that the cytokine interleukin (IL)-11 – through its shared gp130 receptor, the associated Jak kinases and Stat3 signaling – promotes tumourigenesis. We continue to make inroads in better understanding the mechanisms by which the IL11-gp130-Stat3 signalling cascade in non-transformed cells in the immediate environment of tumours fuels tumour growth and prepares the metastatic niche. These and other insights are currently being assessed against findings in human tumours to help better predict the relative risk of disease progression of cancer patients, focussing on colon cancer as one of the major health burdens.