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Predicting Responsiveness of Breast Cancers to Polyamine-type Chemotherapy





Joe Gray and colleagues at Berkeley Lab have developed procedures for identifying which subtypes of cancers are most sensitive to polyamine-type chemotherapeutic agents and for guiding the selection of complementary therapeutic agents. Polyamines regulate important cellular functions, particularly in mammalian cells, and dysregulation of polyamines occurs frequently in cancer.

The Berkeley Lab team used a systems approach to study the relative effects of polyamine analog PG-11047 on breast cancer cells derived from different patients. Using a panel of 48 breast cell lines in an in vitro assay, the team developed a 13-gene marker set that can be used to identify a subset of breast cancer patients who may respond well to treatment with this analogue. Basal-like tumor cells, in particular, seem more responsive to this compound. This set of markers could be useful in selecting patients for further evaluations of PG-11047.

Breast cancers have been classified into five distinct subtypes associated with various tumor characteristics and clinical outcomes: basal-like, luminal A, luminal B, ERBB2+, and normal breast-like. With hundreds of candidate therapeutic agents now under development, a process is needed to assess which drugs work best for each subtype and to develop assays for selecting patients for the resulting clinical trials. The biopharmaceutical industry can use the Berkeley Lab technology to improve clinical trial design and response rates for therapeutic agents that target particular breast cancer subtypes.

DEVELOPMENT STAGE:  Proven principle.   

STATUS:  Published PCT patent application # WO/2009/055823 available at Available for licensing or collaborative research.


Kuo, Wen-Lin, Das, Debopriya, Ziyad, Safiyyah, Bhattacharya, Sanchita, Gibb, William J., Heiser, Laura M., Sadanandam, Anguraj, Fontenay, Gerald V., Hu, Zhi, Wang, Nicholas J., Bayani, Nora, Feiler, Heidi, Neve, Richard M., , Wyrobek, Andrew J., Spellman, Paul T., Marton, Laurence J., and Gray, Joe W. A systems analysis of chemosensitivity of breast cancer cells to the polyamine analogue PG-11047, BMC Medicine 2009, 7:77.


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Comprehensive Prognostic Markers and Therapeutic Targets for Drug-Resistant Breast Cancers, IB-2281

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

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


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