|A new cancer drug, DTP3, kills myeloma|
cells in laboratory tests.
Scientists have developed a new cancer drug which they plan to trial in multiple myeloma patients by the end of next year. In a paper published today in the journal Cancer Cell, the researchers report how the drug, known as DTP3, kills myeloma cells in laboratory tests in human cells and mice, 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, which accounts for nearly two per cent of all cancer deaths.
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, and 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.
The researchers 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, that 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 over 20,000 molecules and found two that disrupted the protein complex. Further refinements led to the experimental drug, DTP3, which tests showed kills cancer cells very effectively but appears to have no toxicity to normal cells at the doses that eradicate the tumours in mice.