How does DTP3 work?
Myeloma is a type of blood cancer that starts in the bone marrow where blood cells are made. Cancerous myeloma cells can appear simultaneously in the marrow of different bones and spread from one location to another. That is why the disease is often called multiple myeloma.
DTP3 is a small molecule that inhibits two proteins, GADD45b and MKK7, which are part of a signaling pathway called the NF-kB pathway. This pathway is vital to all cells, but is overactive in cancerous cells, promoting the spread and growth of cancer. While this pathway has been known for some time, targeting it in cancer cells without affecting healthy cells has been challenging.
Researchers have discovered that GADD45b and MKK7 are downstream of NF-kB and specific to cancer cells. By blocking or inhibiting these two proteins, NF-kB signaling can be halted. Therefore, because GADD45b and MKK7 are specific to cancer cells, DTP3 should only affect these cells and not healthy ones.
Preclinical studies in mouse tumors have yielded promising results.
DTP3 in clinical trials
A Phase 1/2a pilot trial (EudraCT 2015-003459-23) tested the safety and effectiveness of DTP3 treatment in three patients with relapsed or refractory myeloma, who had received at least two prior lines of therapy but whose cancer was still progressing.
The patients received either 0.5, 1, or 2 mg/kg doses of DTP3 as an intravenous infusion three times a week for four weeks.
The results of the study were published in the British Journal of Haematology. Treatment with DTP3 was able to halt cancer progression in two of the three patients. Researchers hypothesized that the reason why one patient did not respond to the treatment while the other two did was the difference in the amount of GADD45b protein between patients. Based on these findings, they suggested that patients in future studies should be screened for the amount of GADD45b they have prior to treatment.
DTP3 therapy was found to be well-tolerated and had no adverse effects or signs of significant toxicity.
Last updated: Jan. 29, 2020
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