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Combination of Anti-cancer Medications and Markers for Improved Therapeutic Response




Scientists at Berkeley Lab have identified a new combination of drugs that inhibit the growth of cells from HER2-positive breast cancers as well as markers that predict sensitivity to the combination. This may lead to improved efficacy and reduced toxicity in the treatment of these aggressive tumors that affect approximately 20% of patients with breast cancer.

The scientists tested greater than 20 breast cancer cell lines and found that lapatinib and an AKT inhibitor showed a significant synergistic interaction in inhibiting growth of cells with PIK3CA gene mutations. These mutations were also associated with high levels of SASH1 gene expression. However, the drugs had an antagonistic effect on each other in wild-type PIK3CA cells. But, when a wild-type cell line was transduced with a PIK3CA mutation, it became susceptible to treatment. These results suggest that the presence of PI3K pathway mutations and/or high expression of SASH1 in HER2-positive tumors would predict that the patient would be responsive to the new combination therapy.

Patients with HER2-positive breast tumors are usually treated with trastuzumab or lapatinib, but many tumors are not responsive or develop resistance to these agents. The Berkeley Lab discovery represents an important advance by identifying a new combination of targeted therapeutic agents with potential clinical efficacy, and biomarkers that predict which patients are most likely to respond to this therapy. Other combinations of drugs in the same classes may be effective against these and other types of cancers that can be HER2 positive, such as those of the ovary, stomach, and endometrium.

DEVELOPMENT STAGE: In vitro inhibition in tumor cell lines.

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


ANXA9: A Therapeutic Target and Predictive Marker for Early Detection of Aggressive Breast Cancer, JIB-2371

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

Predicting Responsiveness of Breast cancers to Polyamine-type Chemotherapy, WIB-2423


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