TriStar Technology Group (Rockville, Maryland) said that the results of a genetic study by a German academic partner could have “major implications” in the treatment of breast cancer, with potential for a companion drug/diagnostic under the broad umbrella of personalized medicine.

The research, which was carried out using TriStar’s high-throughput tissue analysis platform and conducted by its collaborator, the University Medical Center Hamburg-Eppendorf (UKE) in Germany, found that one-fifth of women with breast cancer carry extra copies of a particular gene (ESR1).

These research results were presented Tuesday in a poster presentation at the American Association for Cancer Research (AACR; Philadelphia) meeting in Los Angeles. The study was published online in Nature Genetics on April 8.

Milan Bhagat, president of TriStar Technology, told Diagnostics & Imaging Week that the research finding is the “most unique” discovery by the company, though it is by no means the first. The company performs fee-for-service contract work for its clients in “numerous studies” each year, he said.

However, in this instance, TriStar used its platform technology for its own internal uses, and Bhagat said he believes the study’s findings have potential for a development of a companion drug and diagnostic.

The study, “Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer,” was co-authored by Ronald Simon, UKE’s/TriStar’s head of molecular pathology, and Guido Sauter, TriStar’s co-founder and chief scientific officer.

Their research found that 20% of breast cancer patients carry extra copies of a gene called ESR1 (estrogen receptor alpha), and that these patients are more likely to respond positively to the estrogen-blocking drug tamoxifen than are patients who do not carry extra copies of the gene.

“The findings of this study could lead to genetic tests to determine when and whether tamoxifen should be prescribed as an effective breast cancer treatment,” said Simon. “The findings also suggest that tamoxifen might, one day, replace or diminish the need for chemotherapy in some women.”

Sauter also said that the gene is amplified in women with certain precancerous conditions; therefore, “tamoxifen might also help prevent breast cancer from developing in women showing its early signs.”

With this particular research, Bhagat said TriStar Technologies is seeking to license out the technology for the development of a diagnostic.

The difference between this research and previous studies, Bhagat said, is that, previously, the company focused on the detection of gene expression by immunohistochemistry.

“This study doesn’t look at gene expression; it looks at gene amplification using FISH [fluorescence in situ hybridization] which is a far more reliable technique . . . ,” he said, noting that it is a “much more reliable predictor of diagnostic benefit.”

FISH technology is designed to identify chromosome aberrations associated with various diseases.

The study says: “Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha.”

The study also says that estrogen receptor is “one of the most important therapeutic targets in breast cancer.”

According to the study, which cites other research, “more than two-thirds of breast cancers show estrogen receptor expression at the time of diagnosis . . .”

The researchers completed tissue microarray analysis of more than 2,000 clinical breast cancer samples, which “showed ESR1 Amplification in 20.6% of breast cancers.”

“Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification,” the study says. “In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification.”

Bhagat said the company would also be interested in partnering with a pharma company to develop a drug, should ongoing studies point them in that direction. In fact, in other studies, this same ESR1 gene has demonstrated “potential as a therapeutic.”

The TriStar high-throughput tissue analysis platform is designed to enable researchers to rapidly screen genes against thousands of tissue samples, representing numerous types of cancers, to identify genetic markers, validate drug targets that cause disease and correlate clinical data thereby accelerating the development of new and safer drugs.

“We have, if not the largest, then one of the largest commercially available repositories of microarray formalin fixed and frozen human tissue microarrays in the world,” Bhagat told D&IW. “We have these at four centers: three in Europe and one in the U.S., the largest of which is in Europe.”

The findings are used to generate intellectual property either for TriStar or for its collaborators.

Estimates indicate that breast cancer is responsible for 350,000 deaths per year in women worldwide.

In other news from the AACR meeting:

• Immunicon (Huntingdon Valley, Pennsylvania) will exhibit its Immunicon Pharma ServicesSM, the new CellCapture CTC Mouse/Rat Kit and the new EasyCount System at its exhibit booth.

The CellCapture CTC Mouse/Rat Kit is designed to enable pre-clinical studies using animal models. It uses a manual test procedure to capture CTCs in a few drops of mouse blood and the cells are counted and characterized using the CellTracks Analyzer II. This kit is intended to enable scientists to conduct efficacy studies in very early drug studies and may streamline this phase of drug development.

The EasyCount System is a fluorescent microscopy-based imaging system designed to accurately count dead and live nucleated cells and automatically calculate cell viability, in a single test.

Immunicon develops cell- and molecular-based human diagnostic and life science research products and is providing certain analytical services to pharmaceutical and biotechnology companies to assist them in developing new therapeutic agents, with an initial focus on cancer disease management.

• Introgen Therapeutics (Austin, Texas) reported updated Advexin biomarker data over the weekend at AACR. The company is developing molecular therapeutics, immunotherapies, vaccines and nano-particle tumor suppressor therapies to treat a wide range of cancers using tumor suppressors, cytokines and genes.

Abnormality of the p53 tumor suppressor is one of the most common and fundamental molecular defects in cancer, according to Introgen. Advexin is targeted to restoring p53 tumor suppressor function and the detection of abnormal p53 is a logical predictive biomarker for Advexin efficacy, the company noted. In a study of 28 recurrent head and neck cancer patients in Phase II clinical trials, abnormal p53 was shown to correlate with increased survival and tumor responses following Advexin treatment.

Also at the conference, data was presented regarding Introgen’s other Phase III product, INGN 241, indicating that inhibitors of a class of stress proteins called heat shock proteins enhances INGN 241-mediated tumor cell death.

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