Lysyl oxidase (LOX) Inhibitors

LOX is a protein that is produced and secreted by tumour cells, in response to hypoxia-inducible and other factors, leading to increased invasion and the promotion of the ’metastatic niche‘, thereby enabling the formation of metastases at distant sites. LOX is an extracellular copper enzyme that catalyses the formation of reactive species from lysine residues in collagens and elastin in the extracellular matrix, which results in cross-linking of the proteins.

LOX is often increased in hypoxic primary tumours, for example breast and head and neck cancers.

Figure 2 mechanism of metastasis promotion and tumour invasion by LOX.

Patients with high LOX levels in their primary tumours tend to experience low overall survival. We are collaborating with Dr Janine Erler, a world expert in LOX, who has demonstrated that inhibition of LOX can substantially reduce metastasis in model systems. Dr Erler has also demonstrated that in models of breast and colon cancer, blocking LOX function decreased the formation and growth of metastases.

We have also been working with Dr Erler and Professor Marais to discover novel inhibitors of LOX. We are currently working on four series of selective LOX inhibitors.