(The Salt Lake Tribune) -- A discovery of the "on, off" switch for a certain protein has given doctors the clearest picture yet of why normal cells sometimes change and grow into cancer, says a Utah study on ovarian tumors.

If the tumor findings hold up to further scrutiny, then experimental drugs called protein inhibitors (HDAC inhibitors) could be refined to halt cancer before it really starts. LDS Hospital researchers who authored the study used HDAC inhibitors on clumps of ovarian tumor cells in the laboratory. They noted that cancer inhibitor-drug clinical trials are already underway elsewhere in the United States, some involving human subjects, but their study is the first to reveal the biological mechanism that stalls cancerous growth.

"To me, as a clinician, this is very exciting," said oncologist Clyde Ford, part of the LDS Hospital team that examined one type of HDAC inhibitor and its ability to block the proliferation of ovarian cancer cells in the lab. Led by LDS Hospital molecular biologist Kevin Strait, the team published its findings in today's issue of the journal Molecular Cancer Therapeutics.

"The molecular pathways of ovarian cells is not well understood and the fact they're pretty resistant to known chemotherapy agents is the exciting hook here," said Huntsman Cancer Institute's Don Ayer, who was not involved in the research.

Ayer is an investigator in the field of cancer genes and protein activity; once shown the LDS Hospital study, he praised the results.

However, Ayer said the findings would need to be replicated with other kinds of tumor cells before doctors know more about the safety of HDAC inhibitors in humans. "The jury is still out on whether they have too many side effects," he said of the drugs.

The LDS Hospital team found that treating lab-cultured ovarian cells with the experimental compound caused an overnight shutdown of the cells' ability to multiply. This shutdown was the direct result of the drug's ability to "switch on" a protein gene called p21. For some reason, p21 is in the "switch off" position in ovarian cells that have become cancerous.

"There are a number of cancer cells (besides ovarian) in which p21 is defective," Strait said. "This compound basically turns the genes back on" so that the cells act more like normal cells that do not grow uncontrollably.

Basic science research such as the LDS Hospital study is helping to paint a picture of cancer development, showing a single cell exposed to some biochemical force, which causes a mutation in one of a small number of important genes. That mutation leads to uncontrollable cell growth, a hallmark of cancer.

Tumors are most deadly when they become malignant, which is the cells' ability to invade surrounding tissue and break off to travel around the body in blood vessels or through the lymphatic nodes.

Another study in today's New England Journal of Medicine finds the protein cyclin E can help doctors tell which women in the early stages of breast cancer need surgery plus chemotherapy and which ones just need the tumor removed.

That is because cyclin E appeared six times more powerful a predictor than the current methods -- measuring tumor size and how far cancer cells have spread, wrote the New England Journal study's lead author, Khandan Keyomarsi of M.D. Anderson Cancer Center in Houston.

LDS Hospital's Strait said future HDAC inhibitors studies will need to focus on related cells gathered from tumors in breast, colon and pancreas cancers.

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