Warning, careful! regarding Herceptin resistance

[Lani]

Read carefully as it says in METASTATIC patient--our site includes many whose life stories prove otherwise!

1: Nat Clin Pract Oncol. 2006 May;3(5):269-280. Related Articles, Links

Mechanisms of Disease: understanding resistance to HER2-targeted therapy in human breast cancer.

Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ.

R Nahta is Instructor at the Department of Breast Medical Oncology, D Yu is Professor at the Departments of Surgical Oncology and Molecular and Cellular Oncology, M-C Hung is Chairman and Professor in the Department of Molecular and Cellular Oncology, GN Hortobagyi is Chairman and Professor in the Department of Breast Medical Oncology, and FJ Esteva is Director of the Breast Cancer Translational Research Laboratory and Associate Professor, Departments of Breast Medical Oncology and Molecular & Cellular Oncology, all at The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Trastuzumab is a monoclonal antibody targeted against the human epidermal growth factor receptor (HER) 2 tyrosine kinase receptor, which is overexpressed in approximately 25% of invasive breast cancers. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, however, demonstrate disease progression within 1 year of treatment initiation. Preclinical studies have indicated several molecular mechanisms that could contribute to the development of trastuzumab resistance. Increased signaling via the phosphatidylinositol 3-kinase/Akt pathway could contribute to trastuzumab resistance because of activation of multiple receptor pathways that include HER2-related receptors or non-HER receptors such as the insulin-like growth factor 1 receptor, which appears to be involved in a cross-talk with HER2 in resistant cells. Additionally, loss of function of the tumor suppressor PTEN gene, the negative regulator of Akt, results in heightened Akt signaling that leads to decreased sensitivity to trastuzumab. Decreased interaction between trastuzumab and its target receptor HER2, which is due to steric hindrance of HER2 by cell surface proteins such as mucin-4 (MUC4), may block the inhibitory actions of trastuzumab. Novel therapies targeted against these aberrant molecular pathways offer hope that the effectiveness and duration of response to trastuzumab can be greatly improved.

PMID: 16683005 [PubMed - as supplied by publisher]

Hesitated to post, especially as I cannot as yet access the full article to let everyone know what new therapies they believe offer the hope (hopefully lapatinib, as it is the closest to becoming available or something else already FDA approved)