Combination therapy may fight cancer better


Combination therapy may fight cancer better

According to a study published February 29, online in the journal PLoS One, cancer cells appear to be protected from "cell-suicide" by a molecule found at elevated levels in the cancer cells. Normally "cell-suicide" is activated by radiation or chemotherapy.

The study was conducted by researchers at the University of Illinois at Chicago College of Medicine and funded by grants from the National Institutes of Health. First author on the report is Marianna Halasi, a UIC graduate student in biochemistry and molecular genetics.

Andrei Gartel, UIC associate professor of biochemistry and molecular genetics and medicine and lead researcher of the study, explained that the study indicates that two prevalent cancer-fighting techniques may have "tremendous synergy" if used together.

Impairment to the DNA of a cell can cause an avalanche of signals that activates apoptosis (programmed cell death). Although several chemotherapy agents and radiation therapy target and impair DNA somewhat selectively in rapidly dividing cells, making them helpful in fighting cancer, over the course of the treatment several cancer cells become resistance and obstruct the suicide pathway.

Gartel, and his colleague set out to determine if a protein molecule in cancer cells called FOXM1 might play a role in protecting cancer cells from cell suicide, based on the observation that FOXM1 is elevated after DNA damage.

The team used different methods, in order to lower the level of FOXM1 in human cancer cells that were exposed to either chemicals or radiation to impair DNA.

Gartel explained:

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

The researchers found that no matter what technique they used to decrease FOXM1 or what caused the DNA impairment, the results were the same. The team demonstrated that FOXM1 short-circuits cell suicide by restricting the activity of JNK, another protein which triggers cell death, as well as by turning up Bcl-2, an anti-apoptosis protein.

Although chemotherapy drugs and radiation have been used for a long time to treat cancer, proteasome inhibitors (a newer class of chemotherapy agents) appear promising. According to Gartel, all know proteasome inhibitors (some of which are already approved by the FDA for cancer treatment) decrease FOMX1 levels.

Gartel explains that combining proteasome inhibitors with standard chemotherapy drugs, may improve the effectiveness of the drugs.

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Section Issues On Medicine: Disease