Intrinsic and acquired resistance to Her2 targeted therapy...
 

Crit Rev Oncog. 2012;17(1):1-16.
Intrinsic and Acquired Resistance to HER2-Targeted Therapies in HER2 Gene-Amplified Breast Cancer: Mechanisms and Clinical Implications.
Rexer BN, Arteaga CL.
Source
Departments of Medicine and Cancer Biology; Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center; Vanderbilt University School of Medicine, Nashville, TN.
Abstract
Approximately 25% of human breast cancers overexpress the HER2 (ErbB2) proto-oncogene, which confers a more aggressive tumor phenotype and associates with a poor prognosis in patients with this disease. Two approved therapies targeting HER2, the monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib, are clinically active against this type of breast cancer. However, a significant fraction of patients with HER2+ breast cancer treated with these agents eventually relapse or develop progressive disease. This suggests that tumors acquire or possess intrinsic mechanisms of resistance that allow escape from HER2 inhibition. This review focuses on mechanisms of intrinsic and/or acquired resistance to HER2-targeted therapies that have been identified in preclinical and clinical studies. These mechanisms involve alterations to HER2 itself, coexpression or acquisition of bypass signaling through other receptor or intracellular signaling pathways, defects in mechanisms of cell cycle regulation or apoptosis, and host factors that may modulate drug response. Emerging clinical evidence already suggests that combinations of therapies targeting HER2 as well as these resistance pathways will be effective in overcoming or preventing resistance.

Sci Transl Med. 2012 Mar 28;4(127):127rv2.
Improving Treatment of HER2-Positive Cancers: Opportunities and Challenges.
Stern HM.
Source
Department of Research Pathology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA. stern.howard@gene.com.
Abstract
Amplification of the ERBB2 gene, which encodes human epidermal growth factor receptor 2 (HER2), causes the overexpression of a major proliferative driver for a subset of breast and gastric cancers. Treatments for patients with HER2-positive cancer include the monoclonal antibody trastuzumab and, in the case of metastatic breast cancer, the tyrosine kinase inhibitor lapatinib. Despite significant improvement in patient outcome as a result of these therapies, challenges remain. This Review focuses on proposed mechanisms of action and resistance in the context of potential new therapeutic options. Therapeutic approaches currently in development likely will yield additional clinically meaningful improvements for patients with HER2-positive cancer.

Re: Intrinsic and acquired resistance to Her2 targeted therapy...
 

Another abastract posted by Lani not long ago:

http://her2support.org/vbulletin/sho...eted+Therapies