ROANOKE TIMES Copyright (c) 1996, Roanoke Times DATE: Thursday, June 13, 1996 TAG: 9606130051 SECTION: NATIONAL/INTERNATIONAL PAGE: A-3 EDITION: METRO DATELINE: PHILADELPHIA SOURCE: Associated Press
Discoveries of how cells fight off cancer have led to the development of a possible test to tell how aggressive a patient's lung cancer is - and perhaps even predict who is most susceptible to tumors.
The test, created by Dr. Antonio Giordano of Thomas Jefferson University in Philadelphia, is supposed to detect levels of a protein important for stopping cancer's uncontrolled cell growth.
The test is not yet available - a Pennsylvania company is preparing to do additional studies required for Food and Drug Administration approval.
But Giordano says the test is a first step. Ultimately, he hopes new findings on the different molecules involved in a cell's life cycle, including this Rb protein, will lead to a genetic therapy for lung cancer.
``That is many years away,'' acknowledged Giordano, who plans next month to report findings on 200 patients given his Rb test. He gave a preview Wednesday at a meeting of biotechnologists.
More immediately, if additional studies prove the test works, he said doctors may use it to help decide how aggressively patients should be treated.
``I understand ... this is still evolving,'' said study participant Norman Gross of Wynnewood, Pa., who says his moderate levels of the Rb protein may be one reason his lung cancer has been in remission for a year. ``But I just wanted to know'' the results.
Lung cancer kills 160,000 Americans a year, and cigarette smoking is the chief cause. Research indicates many carcinogens in tobacco smoke can injure genes that, when activated by a mutation, can stimulate the growth of cells that are precursors to cancer.
But cells have built-in safety mechanisms that are supposed to detect such mutations and stop them. These tumor suppressor genes control cell division - unless they are mutated so they don't work, either.
``Can the lack of a single suppressor gene cause cancer? Yes,'' said Dr. Carlos Cardon-Cardo of Memorial Sloan-Kettering Cancer Institute in New York.
The most well-known suppressor gene is p53, but the retinoblastoma gene may be equally important, he said. Originally identified as the cause of a rare eye cancer, mutated Rb genes now have been discovered in breast, prostate, cervical and lung cancers.
Simple cells divide until eventually they are dedicated to a particular function in an organ. Defective Rb appears to allow those ``differentiated cells'' to start reproducing again, opening a path to the uncontrolled cell growth of tumors, said Dr. James DeCaprio of the Dana Farber Cancer Institute in Boston, who is experimenting with Rb in mice.
Adding the Rb gene to human lung cancer cells in test tubes can ``arrest their growth in a dramatic way,'' Giordano said.
So he used an antibody to the protein the Rb gene produces to measure how active the gene was in lung cancer patients.
``There was a strong correlation between aggressive disease and low expression'' of the gene, he explained. So people with low levels might benefit more from stronger - and riskier - therapy, he said.
Additionally, smokers who have low Rb levels probably would be the most at risk of getting lung cancer, he added.
The Rockland Co. of Gilbertsville, Pa., said it plans to seek FDA approval to sell the test within 16 months.
It was unclear how much additional research Rockland will need. Just last December, FDA's scientific advisers rejected a test kit to detect breast cancer patients' levels of a gene believed to spur tumor cell growth. Although several hospitals already offer such a breast test privately, the panel said a study of 244 patients was too small to approve wide sales.
Giordano's eventual goal is to increase patients' Rb levels, to fight growth of existing cancer cells and perhaps even lower susceptible people's risk of getting sick.
But ``getting the healthy gene in will be complex,'' he conceded.
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