Outfoxing the Cancer Fox

Cancer cell protein FOXM1 inhibitors may boost power of chemotherapy

(RxWiki News) Part of the life cycle of a cell - as with every other living thing - is death. Cancer cells have to be pounded by radiation or chemotherapy to die or actually commit suicide. Scientists may have discovered what interferes with that death.

A protein that appears in large quantities in cancer - FOXM1 - apparently outfoxes radiation and chemotherapy, keeping cancer cells from dying.

Researchers may have found a way to outfox FOXM1 so that cancer cells can't take it anymore and keel over dead.

"Ask your oncologist about the latest combination therapies."

University of Illinois at Chicago College of Medicine researchers have discovered that blocking FOXM1, along with radiation and chemotherapy, may be particularly powerful and effective when used together.

Principal study investigator, Andrei Gartel, UIC associate professor of biochemistry and molecular genetics and medicine, observed that DNA damage elevates FOXM1 in cancer cells.

DNA damage triggers a process that's programmed cell death, or apoptosis. Radiation and chemotherapy work by damaging the DNA in cancer cells. However, in time, the cancer cells become resistant to the treatment by scrambling the suicide signaling.

For this study, researchers exposed human cancer cells to either chemicals or radiation to damage the DNA. They then used a number of methods to lower the levels of FOXM1 in the cells. 

"We found a significant increase in DNA-damage-induced apoptosis in cells with diminished levels of FOXM1," Gartel said.

Increased cellular suicide happened regardless of the methods used to cause the DNA damage or lower FOXM1 levels.

A newer class chemotherapy agents called proteasome inhibitors are known to reduce FOXM1 levels. 

Combining these new medications with standard chemotherapy agents could boost the effectiveness of conventional cancer drugs. And the dual therapy may have "tremendous synergy" if used in combination, Gartel says.

This research was published online in the journal PLoS One on February 29, 2012.

The study was supported by grants from the National Institutes of Health.

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Review Date: 
March 5, 2012