New hope for the treatment of Multiple Myeloma
Discovering a new way of tackling cancer of the white blood cells
Professor Guido Franzoso and his colleagues at Imperial College London have discovered a new way of tackling multiple myeloma, an incurable cancer of the white blood cells.
This blood-borne cancer cannot be generally treated using radiotherapy or surgery, and so the options are restricted to chemotherapy or bone marrow transplant. Even the most recent treatments cannot completely destroy the cancer, allowing some of the cancer cells to escape. Whilst the disease can be temporarily stabilised, relapse is unfortunately inevitable. As a result, most of the 110,000 people diagnosed each year with the disease in the US, Europe and Japan will die within a few years of diagnosis.
Professor Franzoso’s team have discovered a new protein, called Gadd45β, which forms one half of a crucial signalling point within cells. An enzyme called MKK7 forms the other half of this signalling point. When Gadd45β and MKK7 bind together, they stop the signals that tell the cancerous cells to activate a form of cellular suicide known to specialists as ‘apoptosis’. The binding of these two proteins together allow cancerous cells to multiply uncontrollably.
The Imperial team has developed a novel compound molecule, called DTP3, that disrupts the interaction between Gadd45β and MKK7, which results in the cancerous cells being effectively killed. Crucially, the drug is not toxic to the normal cells. This unique property makes DTP3 an exciting starting point in the search for a new effective drug therapy against multiple myeloma.
The research team has now initiated tests of the drug in man to develop a safe and effective therapy to treat patients suffering from multiple myeloma and potentially other cancers. The first of such clinical studies in patients with multiple myeloma has recently begun, with funding from the Medical Research Council (MRC). This study is currently open for recruitment at Imperial College London, and will soon be opening in other Centres in London. Additional clinical studies of the drug are being planned in the US by the spinout company, Kesios Therapeutics, which was formed to commercialise DTP3 and other similar drugs, based on the research conducted by Professor Franzoso’s team.
Cancer-selective targeting of the NF-kB survival pathway with GADD45β/MKK7 inhibitors. L. Tornatore, A. Sandomenico, D. Raimondo, C. Low, A. Rocci, C. Tralau-Stewart, D. Capece, D. D'Andrea, M. Bua, E. Boyle, M. van Duin, P. Zoppoli, A. Jaxa-Chamiec, A.K. Thotakura, J. Dyson, B.A. Walker, A. Leonardi, A. Chambery, C. Driessen, P. Sonneveld, G. Morgan, A. Palumbo, A. Tramontano, A. Rahemtulla, M. Ruvo, G. Franzoso. 2014.Cancer Cell, 26: 495-508.
* FEATURED ARTICLE: 2014. Cancer Cell, 26: 495-508.
* Previews: 2014. Cancer Cell, 26: 447-449.
Watch: 2014. Cancer Discovery, 4: 1365.