New Cancer Drug Combination Shows Promise

A new combination of cancer treatment drugs has been shown to effectively kill colon, liver, lung, kidney, breast and brain cancer cells while having little effect on noncancerous cells, according to researchers at Virginia Commonwealth University Massey Cancer Center, where the treatment is being developed.

The next phase of researching the treatment will involve a clinical trial in a small group of patients.

"It is still too premature to estimate when a clinical trial will open to further test this drug combination therapy, but we are now in the planning phase and encouraged by the results of these laboratory experiments," said Andrew Poklepovic, an oncologist and member of the Developmental Therapeutics research program at VCU Massey Cancer Center. "We are also encouraged by the fact that the drugs used in this therapy are either already approved by the FDA to treat certain cancers or are currently being investigated in other clinical trials."

A combination of the drugs sorafenib and regorafenib synergize with a class of drugs known as PI3K/AKT inhibitors have been shown to kill a variety of cancers, the researchers report in the journal Molecular Pharmacology.

In a statement the researchers said:

"Sorafenib and regorafenib work by blocking the production of enzymes called kinases, which are vital to the growth and survival of cancer cells. Sorafenib is currently approved by the FDA to treat kidney and liver cancers, and regorafenib is currently approved for the treatment of colorectal cancer. However, sorafenib and regorafenib do not directly affect PI3K and AKT kinases, which are also very active in promoting cancer cell survival. The addition of a PI3K/AKT inhibitor to the combination of sorafenib and regorafenib dramatically increased cell death and was even effective against cells with certain mutations that make one or the other drug less effective."

Paul Dent, the leader of the study and a Universal Corporation Distinguished Professor for Cancer Cell Signaling and member of the Developmental Therapeutics research program at VCU Massey Cancer Center as well as vice chair of the Department of Neurosurgery at VCU School of Medicine, said:

"We know that there are certain cellular processes that are frequently dysregulated in cancers and important to cell proliferation and survival, but if you shut down one, then cells can often compensate by relying on another. We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive."

The treatment killed cancer cells by "physically interacting with molecules to block the survival pathways and induce a toxic effect known as autophagy," which is a process where cells metabolize themselves when they become starved of the resources they need to survive.

"Many groups are trying the approach of inhibiting two survival signaling pathways, but our approach takes this further by blocking significantly more of these pathways," Dent said. "Our findings could benefit many different cancer patients based on the broad range of effects seen in multiple cancer types."