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Biomarkers for Predicting Breast Cancer Patient Response to PARP Inhibitors

JIB-3095

APPLICATIONS OF TECHNOLOGY:

ADVANTAGES:

ABSTRACT:

Researchers at Berkeley Lab, UC San Francisco (UCSF), and Oregon Health & Science University (OHSU) have discovered eight biomarkers that may be used to predict whether a breast cancer patient will benefit from PARP inhibitor therapy. The invention can be used to improve the cost-effectiveness of clinical trials by targeting breast cancer patients who respond well to PARP-inhibitor treatments. The invention also promises to be an effective companion diagnostic for drug companies when testing breast cancer patient response to PARP-inhibitor therapy.

PARP inhibitors destroy breast cancer cells by blocking PARP or poly (ADP-ribose) polymerase – an enzyme used by all cells in the normal process of repairing themselves – from binding to the cell’s damaged DNA. Despite their promise to make chemotherapy treatments more effective for patients with chemo-resistant cancers, PARP inhibitors currently available through clinical trials are based on a single gene/biomarker that targets only those patients with BRCA1/2-mutated and triple negative breast cancers, which is less than 5% of all breast cancer cases. In contrast, the new eight-gene signature may broaden the scope of eligible patients to approximately 20% of all breast cancer cases. The invention’s wide outreach may reduce clinical trial costs by a factor of 2 or more, a significant saving considering that a single clinical trial can cost as much as $100 million.

The Berkeley Lab/UCSF/OHSU invention is the first system designed to predict PARP sensitivity in a broad scope of breast cancer patient populations. In a study involving a set of 22 breast cancer cell lines, the inventors restricted the pool of potential biomarkers to genes involved in DNA repair pathways. Biomarkers that were consistently associated with response to PARP inhibitor therapy in the cell lines were combined in a weighted voting algorithm to predict whether patient cells expressing for certain genes would be sensitive or resistant to PARP inhibitors.

The invention may identify eligible cancer patients for PARP-inhibitor treatment by testing a patient’s breast cancer tissue for amplification or expression in at least one of the signature’s eight genes. When at least one gene or gene product is amplified in response to a PARP inhibitor, the patient is predicted to be sensitive or resistant to PARP-inhibitor therapy.

As a companion diagnostic, the invention may also help pharmaceutical companies meet federal requirements for proving PARP-inhibitor effectiveness in specific breast cancer populations..

DEVELOPMENT STAGE:  Proven principle 

STATUS: Patent pending. Available for licensing or collaborative research.

FOR MORE INFORMATION:

Turner, N.C., Ashworth, A., “Biomarkers of PARP inhibitor sensitivity,” Breast Cancer Res Treat, 2011 May; 127(1): 283-6. Epub 2011 Feb 8.

Wang, X., Weaver, D.T., “The ups and downs of DNA repair biomarkers for PARP inhibitor therapies,” Am J Cancer Research 2011; 1(3): 301-327.

Liang, H., Tan, A.R., “PARP inhibitors,” Curr Breast Cancer Rep, (2011) 3: 44-54

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

Genetic Profile Determines Prognosis and Response to Cancer Therapy, WIB-2709

REFERENCE NUMBER: JIB-3095

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