New studies in cell lines suggest that the combination, which targets a common gene pathway in colon cancer cells, could be more potent than either drug alone, and has fewer side effects.
By itself, interferon’s cell-killing activity is non-specific in targeting a variety of cells and cell-based gene activity, causing serious side effects such as heart failure and low blood counts, in addition to killing cancer cells. However, scientists have recently found one factor in interferon’s makeup that could have cancer-killing qualities, but with fewer side effects since it activates fewer genes.
The researchers discovered that IRF5 (Interferon Regulatory Factor-5), which works as a tumor suppressor to halt cancer cell growth, is turned off by many cancers, but low levels of the suppressor protein are found in most colon cancers.
On further investigation the researchers found that although interferon boosts IRF5 protein levels in colon cancer cells, it does not raise it enough to kill the cells. To boost IRF5 levels, the investigators combined interferon with the chemotherapy drug, irinotecan, a treatment that damages DNA in rapidly dividing cells, rendering them unable to divide.
When irinotecan and interferon were combined more than 80% of colon cancer cells with IRF5 proteins died. To demonstrate the importance of IRF5 to this process the researchers compared the combination with the IRF5 protein removed. In this instance only 28% of cells died.
Cancers lacking tumor suppressor genes and the proteins they make are often difficult to treat because cells are unable to put the brake on abnormal growth. This study indicates that IRF5 applies the brakes even in the absence of other tumor suppressor genes.