Inventor's corner: novel targed drugs for treating multiple myeloma

Professor Guido Franzoso leads a research group developing novel drugs for the treatment of blood-based cancers, in particular multiple myeloma.

How do you go about tackling these blood cancers, which by their nature are dispersed and difficult to get at?

I began by trying to understand a protein complex called nuclear factor-kappa B (NF-KB), which controls a very important gene signalling pathway responsible for the body’s response to inflammation and infection. Many types of tumours show activation of this pathway so we wanted to get to the bottom of it. I was interested in the ‘downstream’ genes and encoded proteins that NF-KB activates to drive tumour development and inflammation.

What did you find?

A key protein called Gadd45beta, which prevents the death of tumour cells by binding to and inhibiting its partner MKK7, a protein responsible for cell death. We have now developed a series of drugs that de-stabilise this partnership, leaving MKK7 free to destroy tumour cells.

How is this different from current approaches?

Not one NF-KB inhibitor developed to date has been effective in killing tumour cells without also causing harm to normal healthy cells, which has very undesirable side effects for the patient. While Gadd45beta is highly active in the cancer cells of multiple myeloma patients, it is silent in many normal cells, so by targeting its gene we have demonstrated a truly disease specific approach.

What’s next?

Following very promising pre-clinical studies, the next step is to proceed with phase l and phase lla clinical trials in multiple myeloma, with the support of a substantial MRC translational grant. Additionally, through Kesios the Imperial spin-out company we formed last year, we have started a programme that will build a pipeline of Gadd45beta targeted therapeutics tackling a broader range of cancers.

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