Treatment inhibits key process that enables cancer cells to multiply.


Researchers in London plan to begin clinical trials on a significant new treatment for multiple myeloma by the end of next year.

In laboratory testing, the drug, known as DTP3, killed myeloma cells within human cells and mice without causing any toxic side effects. In a paper published on October 13, 2014 in Cancer Cells, researchers outlined how the drug inhibits a key process that allows cancer cells to multiply.

“Lab studies suggest that DTP3 could have therapeutic benefit for patients with multiple myeloma and potentially several other types of cancer, but we will need to confirm this in our clinical trials, the first of which will start next year," said lead researcher Professor Guido Franzoso in a press release.

DTP3 was developed through an evaluation of the mechanisms that enable cancer cells to continue multiplying beyond their normal lifespan. Specifically, the researchers studied a protein called nuclear factor kappa B (NF-kB), which plays a key role in inflammation, in addition to immune and stress response systems.
 
The protein was found to be overactive across many cancer types, and responsible for turning off normal cellular mechanisms that lead to cell death and enables cancer cells to survive.
 
Attempts to develop a treatment that inhibits the protein have been thus far unsuccessful because the drugs also block a number of important processes in healthy cells that are controlled by NF-kB, which causes serious toxic side effects.
 
Through a Biomedical Catalyst funding grant from the Medical Research Council, researchers sought to find target genes that are downstream of NF-kB, which may be responsible for its role in cancer specifically. In cells from multiple myeloma patients, a protein complex was identified that is believed to play a crucial role in allowing the survival of cancer cells.

The researchers screened over 20,000 molecules before finding 2 that safely disrupt the protein complex. Through further refinements, DTP3 was developed.
 
In testing, the drug was found to kill cancer cells effectively with no apparent toxicity to normal cells at the doses found to eradicate the tumors in mice.
 
"We had known for many years that NF-kB is very important for cancer cells, but because it is also needed by healthy cells, we did not know how to block it specifically,” Franzoso said. “The discovery that blocking the GADD45β/MKK7 segment of the NF-κB pathway with our DTP3 peptide therapeutic selectively kills myeloma cells could offer a completely new approach to treating patients with certain cancers, such as multiple myeloma.”