Potential new therapeutic target for drug-resistant cancer

Dr Peter Janes

A group of international scientists, led by researchers from the Biomedicine Discovery Institute (BDI) and the Department of Biochemistry and Molecular Biology at Monash University, have discovered a way to target an active form of a protein called ADAM 10, which is associated with the initiation of cancer and its maintenance in humans and in mouse models.

Importantly the protein appears linked to a cancer cell’s capacity to resist chemotherapy – and, when this target is blocked, regrowth of the tumour post chemotherapy is inhibited.

The discovery, published today in the Journal of Experimental Medicine, reveals a potentially new therapeutic target for tumours that develop drug resistance, including colorectal and breast cancers.

The researchers from Australia and the United States, headed by Dr Peter Janes and the late Associate Professor Martin Lackmann at BDI, have found ADAM 10 is highly active in tumours in mice, particularly in a subset of tumour cells associated with tumour initiation and maintenance, and with drug resistance.

The researchers developed an antibody against the ADAM 10 protein and found that it preferentially targets the active ADAM10 on these cells, and has the capacity to block tumour growth in animal models.

The study importantly also found that the ADAM 10 antibody was most effective in stopping tumour growth when combined with chemotherapy.

According to Dr Janes, the antibody is likely targeting ‘cancer stem cells’, slow-growing cells that escape the chemotherapy. “Although it is still early days, we believe using chemotherapy to knock out the bulk of the tumour followed by selective inhibition of active ADAM 10 to target and kill those cells that escaped chemotherapy has potential as an additional way to treat cancers that develop chemo-resistance.”