APPLICATIONS OF TECHNOLOGY:

		Under a microscope, fluorescent markers (right) reveal amplified genes in the chromosomes of a breast tumor’s cells.

• Identifying patients with breast cancers that are resistant to conventional chemotherapies and developing new treatment strategies for them
• Screening patients with chemo-resistant tumors for clinical trials
• Using gene-specific inhibitors to treat chemo-resistant breast cancers
• Researching cancer progression and remission

ADVANTAGES:

• Defines a more comprehensive set of breast cancer markers linked to drug-resistance than previous studies
• Enables development of a more accurate multi-gene assay to identify patients with breast cancers that are resistant to conventional breast cancer therapies
• Enables the development of potentially more effective therapies through individualized, gene-specific treatments
• Enhances conventional treatments through earlier detection of breast cancer tumors

ABSTRACT:

Joe Gray and his team at Berkeley Lab, in collaboration with the University of California at San Francisco (UCSF), have defined a new set of predictive markers and candidate therapeutic targets for drug-resistant breast cancers. Gray and his colleagues are the first to report that this 66-gene set is linked to chemo-resistant breast tumors and lower survival rates. The group of markers makes it possible to develop a more accurate multi-gene assay to identify patients who are likely to be resistant to conventional breast cancer therapies, design alternative treatments that are more likely to be effective, improve patients’ chances for recovery by early identification, and establish enhanced screening for clinical trials.

In a comprehensive genomic survey that compared genome copy number profiles of 145 primary breast tumors with gene expression profiles of 130 primary breast tumors, Gray and associates identified 66 genes in regions of amplification at four chromosome locations for breast cancers resistant to conventional therapies, such as radiation, surgery, and chemotherapy.

The predictive markers and candidate therapeutic targets that compose the 66-gene set may enable development of an assay that is more comprehensive, and may therefore offer more accurate prognoses, than others currently on the market.  This 66-gene set also broadens the spectrum of potentially new gene-specific cancer therapies.  Of the 66 genes, the Berkeley Lab and UCSF researchers have to date identified nine targets that may be treatable with a gene-specific drug that inhibits cancerous cell growth; in particular, the expression of at least one target can be silenced by the use of small molecules such as siRNAs.

This 66-gene set also offers new statistical procedures to link patients’ resistance to existing treatments (e.g., adriamycin- or cytoxan-based chemotherapies, surgery, radiation), and low survival rates with specific amplification sites, genes, and gene products. It is the most comprehensive set of genes to date in the quest for early, accurate cancer detection, and increased survival rates.

STATUS:

• Published Patent Application WO/2007/143752 available at www.wipo.int. US published patent application, US2009 0203051-A1 available at www.uspto.gov. Available for licensing or collaborative research.

FOR MORE INFORMATION:

Chin, K., DeVries, S., Fridlyand, J., Spellman, P.T., Roydasgupta, R., Kuo, W.-L., Lapuk, A., Neve, R.M., Qian, Z., Ryder, T., Chen, F., Feiler, H., Tokuyasu, T., Kingsley, C., Dairkee, S., Meng, Z., Chew, K., Pinkel, D., Jain, A., Ljung, B.M., Esserman, L., Albertson, D.G., Waldman, F.M., Gray, J.W., "Genomic and Transcriptional Aberrations Linked to Breast Cancer Pathophysiologies," Cancer Cell, Vol. 10, Issue 6, December 2006, 529–541.

Neve, R.M., Chin, K., Fridyland, J., Yeh, J., Baehner, F.L., Fevr, T., Clark, L., Bayani, N., Coppe, J.-P., Tong, F., Speed, T., Spellman, P.T., DeVries, S., Lapuk, A., Wang, N.J., Kuo, W.-L., Stillwell, J.L., Pinkel, D., Albertson, D.G., Waldman, F.M., McCormick, F., Dickson, R.B., Johnson, M.D., Lippman, M., Ethier, S., Gazdar, A., Gray, J.W., "A Collection of Breast Cancer Cell Lines for the Study of Functionally Distinct Cancer Subtypes", Cancer Cell, Vol. 10, Issue 6, December 2006, 515–527

REFERENCE NUMBER: IB-2281

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

• Marker for Human Breast Cancer, IB-1242
• Prognostic for Invasive and Metastatic Cancers, IB-1637
• Breast Cancer Therapy and Potential Method for Enhancing Radiation Sensitivity via Inhibition of ß1 Integrin, IB-1965
• Non-Transgenic Cell Lines for Identifying Target Premalignant Genes, IB-2023
• Rac1b: A Highly Selective Marker and Target for Cancer, IB-2167
• High Selectivity Peptides for Cancer Therapy, Screening for Cancer Therapies, and Therapy Sensitization, IB-2489