Researchers have developed a new drug, DTP3, which targets a critical pathway in multiple myeloma cells. DTP3 has shown promising results both in the laboratory, and in mice. It is now set to begin clinical trials in patients by the end of 2015.
Multiple myeloma is a cancer of the plasma cells in the blood. Some of the symptoms of multiple myeloma can include: nausea, constipation, loss of appetite, fatigue, and weight loss. The causes of multiple myeloma remain unclear, however risk increases with age. There is no cure for multiple myeloma, with current treatment able to achieve temporary remission before the cancer eventually relapses, sometimes with the development of resistance to therapy.
Researchers at the Imperial College London have published a study in the journal Cancer Cell, reporting on the development and investigation of DTP3, a novel drug for use against multiple myeloma. The basis of the drug development was the NFkB pathway, which contributes to the survival and malignancy of a range of cancer cells, including multiple myeloma. There is strong scientific evidence for targeting this signaling pathway as it contributes to the survival of the cancer cells. While there has been a lot of focus on developing specific NFkB inhibitors, the obstacle has been the approval of these drugs, since they cause toxicity in normal cells as well as cancer cells. This is due to the global importance of NFkB signalling. Instead of targeting NFkB specifically, the team in London decided to target a mediator of NFkB signaling further along in the pathway that was more specific to the role of NFkB in multiple myeloma. The aim being that blocking this potential target would more specifically effect cancer cells, and have less of an effect on normal non-cancerous cells.
The team developed DTP3, which inhibits the GADD45B/Mkk7 interaction in multiple myeloma cells. They were able to show that DTP3 was able to kill multiple myeloma cells at very low concentrations. In addition, it was also effective at killing cells derived from multiple myeloma patients, and mouse models, with no apparent side effects.
One of the key findings of the study, the fact that DTP3 did not induce toxic side effects, is something that sets this drug apart from the current ‘gold standard’ treatments for multiple myeloma, Bortezomib.
The team is planning to take DTP3 into clinical trials for multiple myeloma patients by the end of 2015, and have been awarded the Biomedical Catalyst funding from the Medical Research Council.
Tornatore, L, Sandomenico, A, Raimondo, D, Low, C, Rocci, A, Tralau-Stewart, C, Capece, D, D’Andrea, D, Bua, M, Boyle, E, van Duin, M, Zoppoli, P, Jaxa-Chamiec, A, Thotakura, AK, Dyson, J, Walker, BA, Leonardi, A, Chambery, A, Driessen, C, Sonneveld, P, Morgan, G, Palumbo, A, Tramontano, A, Rahemtulla, A, Ruvo, M, Franzoso, G. “Cancer-Selective Targeting of the NF-κB Survival Pathway with GADD45β/MKK7 Inhibitors” Cancer Cell Volume 26, Issue 4,xp495–508, 13 October 2014.
News Release “New cancer drug to begin trials in multiple myeloma patients”Available from:http://www.alphagalileo.org/ViewItem.aspx?ItemId=146123&CultureCode=enLast Accessed: October 15, 2014.
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Written by Deborah Tallarigo, PhD