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Almac Diagnostics Sees Benefit for Test Pipeline in New Ovarian, Breast Cancer Studies


This story was originally posted on June 3.

By Justin Petrone

Almac Diagnostics believes that two recent studies could aid its plans to develop new tests for cancer.

In the studies — both of which were presented at the American Society of Clinical Oncology's annual meeting in Chicago last week — Almac researchers and academic collaborators used the company's Disease Specific Arrays to identify biomarkers associated with ovarian and breast cancer.

The Craigavon, UK-based company's DSA chips are manufactured by Affymetrix.

Richard Kennedy, vice president of experimental medicine at Almac, told BioArray News last week that the studies "highlight the success" the Northern Ireland firm has had working with large formalin-fixed, paraffin-embedded datasets to develop "clinically relevant" biomarkers.

"In both studies we have carried out large-scale profiling and data analysis to find disease subgroups and highlight those that are therapeutically relevant," Kennedy said.

Kennedy said that the study results could be used to develop enrichment tools for clinical trials or could eventually serve as the basis for diagnostic tests.

The aim of the first study was to identify molecular subtypes of ovarian cancer. The researchers first performed microarray expression profiling of a clinical dataset of 363 FFPE patient samples using Almac's Ovarian Cancer Disease Specific Array, according to the project's ASCO abstract.

Led by Charlie Gourley of the University of Edinburgh Cancer Research UK Centre, the researchers identified six molecular subgroups that were "highly associated with histology following unsupervised analysis of the full dataset."

Subsequent analysis of the cancers identified three subgroups with the dominant biology of one of these related to angiogenesis. The researchers hypothesized that subgroup "may be useful in identifying patients more ideally suited to treatment with anti-angiogenic therapeutics," according to a statement.

"We are hopeful that this molecular classification will act as the template for the individualization of ovarian cancer care based upon the biology of the patient’s tumor," Gourley said.

In the second study, Almac scientists studying breast cancer identified a molecular subgroup that is DNA damage-response deficient.

Loss of a functional DNA-damage response, or DDR, sensitizes tumors to DNA-damaging as well as targeted therapeutics such as PARP-1 inhibitors, according to the ASCO abstract. Additionally, there is currently no assay to detect DDR proficiency and guide therapeutic choice, Almac claimed.

The researchers used Almac's Breast Cancer Disease Specific Array to profile a cohort of BRCA mutant-enriched and DDR-deficient primary breast tumor samples. The team used hierarchical agglomerative clustering analysis to identify a molecular subtype characterized by activation of pathways known to respond to DNA damage, according to the abstract.

Additional analysis resulted in a 44-gene signature that is "capable of identifying patients who do not respond to standard DNA damaging chemotherapy with a very high negative predictive value and relative risk," according to the abstract.

Paul Harkin, president and managing director of Almac Diagnostics, said in a statement that both studies have "significant clinical relevance and are likely to be of significant interest to both clinicians and the pharma companies represented."

Kennedy said that the study results will benefit Almac's pipeline in two ways — "in the short term as trial-enrichment tools and in the longer term as independent diagnostic tests." He did not provide a specific development timeline for either scenario.

In particular, Kennedy proposed that the new DDR signature could be developed into a patient-stratification tool for existing chemotherapy or a trial-enrichment tool for DNA-damaging or targeted drugs in development.

"The DNA damage signature is capable of identifying patients who do not respond to standard DNA-damaging agents," he said. "This is likely to be of significant benefit to pharmaceutical and biotechnology companies who are developing DNA-damaging agents as well as new targeted therapies such as PARP inhibitors, CHK1/2 inhibitors, and ATM inhibitors," said Kennedy.

In the short term, the signature can be used for clinical trial enrichment via Almac's US Clinical Laboratory Improvement Acts-compliant facility. Almac opened the lab earlier this year (BAN 4/5/2011).

Parallel to this, Kennedy said that Almac is also converting the DDR signature to a quantitative PCR platform, which could later be developed into a full diagnostic test. He did not elaborate.

The tests would join several that the company is currently developing. The closest to commercialization, ColDx, is for colorectal cancer recurrence. The company said earlier this year that the test is entering its final stages of validation (BAN 3/15/2011).

Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com.