Could New Drug Combination Therapy Tell Cancer to Eat its Own Cells?

A recent study looks at a new drug combination therapy that's currently being developed at Virginia Commonwealth University Massey Cancer Center. This new potential treatment may provide a way for cancer to eat its own cells, benefits such cases as colon, liver, kidney, breast and brain cancer.

"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," Andrew Poklepovic, M.D., oncologist and member of the Developmental Therapeutics research program at VCU Massey Cancer Center and assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine said, via a press release. "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."

Lead study author Paul Dent, Ph.D., demonstrated that the drugs sorafenib and regorafenib synergize with a class of drugs known as PI3K/AKT inhibitors in order to kill a variety of cancers by blocking the production of enzymes called kinases that are vital to the growth and survival of numerous cancer cells. Sorafenib is currently approved by the FDA to treat both kidney and liver cancer, and regorafenib is currently approved for the treatment of colorectal cancer. Yet sorafenib and regorafenib do not directly affect PI3K/AKT inhibitor with the combination of the drugs to dramatically increase cell death.

"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," said Dent, 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. "We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive."

Study findings showed that the combination therapy killed cells through physical interaction with molecules that block the survial of pathways and induce toxic effects known as autophagy. Autophagy is known as a protective process in which cells metabolize themselves and are starved of resoures then need to surive. 

"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," says Dent. "Our findings could benefit many different cancer patients based on the broad range of effects seen in multiple cancer types."

More information regarding the study can be found via the journal Molecular Pharmacology.