Oncor Inc. announced Tuesday that it plans to immediatelyenter clinical trials with its Her-2/neu DNA probe for directdetection of gene amplification in breast cancer cells.

The company expects to file for FDA approval early next year,according to Stephen Turner, company chairman and chiefexecutive.

Oncor simultaneously will begin shipment this week of probes,created from the company's own DNA library, to research labs,including the Mayo Clinic Cytogenetics Laboratory and theUniversity of Southern California (USC) School of Medicine.

With the probe, a clinician can for the first time look at animportant genetic marker directly on breast cell tissue to see ifthe gene is normal, Turner said.

The Her-2/neu is a cancer-causing gene that codes for a growthfactor receptor protein, and may be an important predictor ofbreast cancer outcome. Determining prognosis or predicting theaggressiveness of a breast cancer cell population is difficult,Turner said.

Identification of the Her-2/neu amplified genes correlates withtumor aggressiveness, and clinical studies showed that patientswith amplified Her-2/neu in their breast cancers have a poorersurvival rate.

The marker appears to be a significant diagnostic factor in theearly as well as the late stages of breast cancer, as Her-2/neuamplification in breast cancers has been correlated withincreasing tumor aggressiveness, but not with hormone-receptor status, lymph node involvement, tumor size or age.

Oncor's DNA probe may be useful, but the value of ascertainingHer-2 expression has yet to be determined, and must becompared with other proven factors, such as axillary lymphnodes and the size of the tumor, said Robert Carlson, associateprofessor of medicine at Stanford University. Oncor's studyneeds to be applied to a large test group and appropriatelyanalyzed in conjunction with other factors before theprognostic value of knowing the extent of Her-2 expression canbe determined, he said.

"With the more frequent use of mammography, more breastcancers are detected while very small," said Michael F. Press,associate professor in the department of pathology at the USCSchool of Medicine. "The small amount of tissue in these casescan be a limiting factor in the number and types of testsperformed. This new probe provides an additional tool that Ithink will prove to be very useful in evaluating Her-2/neuamplification in small breast cancers."

The presence of a fluorescent marker on the probe requiresonly a fluorescent microscope to do the analysis, making it verycost- and time-effective for early detection, with resultsavailable within 24 hours. The needle biopsy of the tissue ismounted on a microscope slide, and the DNA probe isintroduced into the cells on the slide.

The fluorescent signals are examined under the microscope,and positive signals appear as yellow dots in the nuclei of thebreast cell. Normally there will be two copies of each gene onthe pair of chromosomes, but multiple yellow cells showamplified sequences of the Her-2/neu gene, which is abnormal.

Other detection tests, such as the Southern blot and the use ofHer-2/neu antibodies, are unable to actually witness geneactivity and are therefore a more indirect means of tissueanalysis.

"Our probe allows for direct analysis for gene amplification,which should be a very precise and unambiguous analysis,"Turner said.

DNA probes are a major target area for the Gaithersburg, Md.-based company, which is developing a series of probes that willbecome routine for early detection of breast cancer and willprovide better data for the clinician. According to Turner, Oncorwill announce the development of its other probes later thisyear.

Turner said that initially the main use of DNA probes will be toupgrade and clarify the mammography system. "Genetic testsfor breast cancer will be a broad market and will include bloodtests for the inherited genes, which is important for cliniciansconsidering the high variability and outcome in the disease."

Approximately one out of every nine women in the U.S. willdevelop breast cancer in their lifetime -- second only to lungcancer.

-- Michelle Slade Associate Editor

(c) 1997 American Health Consultants. All rights reserved.

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