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Revolutionizing Cancer Treatment
CHORI Researchers Discover Novel Target for Cancer Therapy

Two recent publications in Cell Death and Disease and Cell Signaling by CHORI scientist Julie Saba, MD, PhD, and her colleagues, demonstrate the potential for targeting a naturally occurring enzyme, called sphingosine-1 phosphate lyase, or SPL, for both reducing the side-effects of radiation and chemotherapy, and increasing radiation-induced cancer cell death.

“The results of our studies indicate that SPL is an important regulator of the cell’s response to radiation,” says Dr. Saba.
“Increasing the amount of SPL in a cell leads to more cell death after radiation exposure, whereas inhibiting the enzyme increases cell survival and the cell’s ability to repair DNA damaged by radiation.”


While researchers are always working toward an ultimate goal of finding ways to target cancer therapies to specific tumors or specific patients, currently the most effective cancer treatments, including radiation, kill all rapidly growing cells. This includes healthy cells in the gut, bone marrow and reproductive organs, as well as cancer cells. Using SPL as a therapeutic target in patients receiving radiation could be particularly effective, however, because most cancer cells no longer have SPL.

"We believe the elimination of SPL by cancer cells is a genetic change that helps them to grow and become more resistant to chemotherapy and radiation," explains Dr. Saba.

"Using an SPL inhibitor to prevent DNA damage caused by radiation in healthy cells could avoid toxicities such as sterility and gastrointestinal side effects without significantly compromising the ability of the radiation to eliminate the cancer cells."

The primary role of the SPL enzyme is to break down sphingosine-1 phosphate, or S1P. Important studies have shown in the past that S1P protects cells from death and that increasing or decreasing SPL directly regulates S1P levels. Dr. Saba's latest publications however, take this knowledge a step further, by elucidating for the first time the mechanisms by which increasing or decreasing SPL impacts cell survival.

“What ours studies show for the first time is that SPL has an effect on the cellular processes involved in DNA repair and cell cycle progression,” says Dr. Saba.

Read More about Dr. Saba's Novel Cancer Treatment Discovery

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Tuesday, May 17, 2011 8:19 AM

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