Heat shock proteins such as Hsp90 are molecular chaperones, with their expression increased in stressed tissues. They may help tumour cells survive in hostile microenvironments and tolerate internal mutations, so driving tumour growth. Inhibiting such proteins may therefore inhibit growth in a wide range of tumour types.
Over-expressed in cancer cells, Hsp90 is essential for the stability and function of several proteins that are mutated into cancer-driving forms in tumours. Inhibition of Hsp90 has the potential to stop cancer progression at multiple levels by inhibiting cell growth and limitless proliferation, promoting cell death, reversing angiogenesis and restricting invasion and metastasis.
Novartis tested AUY922 in a number of Phase I and Phase II studies in over 700 patients with solid tumours and haematological cancers. Efficacy both as a single agent and in combination with targeted therapies has been demonstrated by Novartis. However, those results were not sufficient enough to trigger the start of a pivotal trial in defined patient population.