The results from a recent preclinical study at Virginia Commonwealth University Massey Cancer Center lays the foundation to plan a future phase 1 clinical trial to test the safety of the therapy 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, assistant professor in the Division of Hematology, Oncology and Palliative Care at VCU School of Medicine.
The study led by Paul Dent demonstrated that the drugs sorafenib and regorafenib synergise with a class of drugs known as PI3K/AKT inhibitors to kill a variety of cancers.
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.
"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.
"We are blocking several of these survival pathways, and the cancer cells are literally digesting themselves in an effort to stay alive," Dent said.
Results showed that the combination therapy killed the cells by physically interacting with molecules to block the survival pathways and induce a toxic effect known as autophagy.
Autophagy is a protective process where cells metabolize themselves when starved of the resources needed to survive. The study was published in the journal Molecular Pharmacology.


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