Scientists have developed a new cancer drug that they plan to trial in multiple myeloma patients by the end of next year.
In a paper published in Cancer Cell (2014; doi:1016/j.ccr.2014.07.027), the researchers from Imperial College London in the United Kingdom reported how the drug, known as DTP3, kills myeloma cells in laboratory tests in human cells and mice. It is reported to do so without causing any toxic side effects, which is the main problem with most other cancer drugs. The new drug works by stopping a key process that allows cancer cells to multiply.
Multiple myeloma is an incurable cancer of the bone marrow. It accounts for nearly 2% of all cancer deaths.
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“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 Guido Franzoso, MD, PhD, from the Department of Medicine at Imperial College London.
The new drug was developed by studying the mechanisms that enable cancer cells to outlive their normal lifespan and carry on multiplying. In the 1990s, a protein called nuclear factor kappa B (NF-kB), which plays an important role in inflammation and the immune and stress response systems, was discovered to be overactive in many types of cancer. It was found to be responsible for switching off the normal cellular mechanisms that naturally lead to cell death. This enables the cancer cells to survive.
The pharmaceutical industry and scientists around the world have invested heavily in research into NF-kB inhibitors, but such compounds have not been successfully developed as therapies because they also block the many important processes controlled by NF-kB in healthy cells, causing serious toxic side effects.
This research team took a different approach, looking for target genes downstream of NF-kB that might be responsible for its role in cancer specifically. By studying cells from multiple myeloma patients, they identified a protein complex, named GADD45β/MKK7, which appeared to play a critical role in allowing the cancer cells to survive.
Searching for a safe way to target the NF-kB pathway, they screened more than 20,000 molecules and found two that disrupted the protein complex. Further refinements led to the experimental drug, DTP3. Tests showed it kills cancer cells very effectively but appears to have no toxicity to normal cells at the doses that 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. The discovery that blocking the GADD45β/MKK7 segment of the NF-kB 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,” said Franzoso.
