New Multiple Myeloma Drug To Enter Clinical Trials

By C. Rajan, contributing writer

Researchers at the Imperial College London have developed a new type of drug for treating multiple myeloma which will enter clinical trials in late 2015. The new drug, DTP3, showed promising results in laboratory tests without any toxic side effects.

DTP3 is a novel D-tripeptide that inhibits a key process which allows cancer cells to multiply and survive. According to the researchers, DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher specificity for cancer cells in vitro.

The research team has received the Medical Research Council’s Biomedical Catalyst funding, which will support the drug’s first clinical trial in multiple myeloma patients, scheduled to start by end of next year.

Lead researcher of the study, Professor Guido Franzoso, Department of Medicine at Imperial College London, said, "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."

Multiple myeloma is a highly metastatic type of blood cancer, which originates in the bone marrow and spreads to the bones to form multiple tumors. The disease is incurable and is responsible for about two percent of all cancer deaths. The American Cancer Society estimates that there will be approximately 11,090 deaths in 2014 due to multiple myeloma.

For their drug development approach, the researchers looked at the protein target called nuclear factor kappa B (NF-kB), which is known to be overactive in many types of cancer and is responsible for switching off the natural cell apoptosis process, thus enabling cancer cells to survive.

While there has been considerable previous research on developing NF-kB inhibitors, these have not led to successful drugs due to non-specificity and serious toxic side effects.

In order to find a safer way to target the NF-kB pathway, the researchers studied cells from multiple myeloma patients and identified a protein complex GADD45β/MKK7 in the pathway, which appeared to be helping the cancer cells to survive.

After screening over 20,000 molecules, the team discovered two compounds that disrupted the protein complex. Following some structural refinements, they obtained the peptide DTP3, which showed excellent cancer fighting ability and did not harm normal cells.

"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," Professor Franzoso said.

Further development and commercialization of DTP3 and other possible drug candidates from Professor Franzoso's research will be performed by a spinout company, Kesios Therapeutics, with support from UK technology commercialization company, Imperial Innovations.

The study is published this week in the journal Cancer Cell.