![]() Indeed, trastuzumab (Herceptin, Genentech, South San Francisco, CA, USA), a humanized monoclonal antibody directed against the extracellular juxtamembrane domain IV of HER2, revolutionized the treatment of HER2-positive breast cancer. In contrast to normal cells which express approximately 20,000 HER2 receptors on the cell membrane, each HER2-positive breast cancer cell expresses approximately one to two million HER2 receptors, making HER2 an attractive candidate for targeted therapy ( 7). HER2-positive breast cancers have historically been associated with decreased relapse free survival, decreased overall survival (OS) and poorer prognosis ( 1, 4- 6). Overexpression of HER2 leads to increased signal transduction and activation of the MAPK and PI3K/Akt pathways ( 3). Accepted for publication Aug 12, 2014.Īpproximately 20% of breast cancers are characterized by amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of HER2, which functions as a driver oncogene for such tumors ( 1, 2). ![]() Keywords: Human epidermal growth factor receptor 2 (HER2) breast cancer antibody-drug conjugate pertuzumab T-DM1 This review presents the mechanisms of action as well as phase I, II and III clinical data describing the safety and efficacy of pertuzumab and T-DM1 for HER2-positive breast cancer. Both pertuzumab and T-DM1 are relatively well tolerated. In addition, ado-trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate linking trastuzumab with the cytotoxic maytansinoid, DM1, is an effective treatment for HER2-positive breast cancer that has progressed on other HER2-directed therapies. The addition of pertuzumab to trastuzumab results in synergistic tumor cell inhibition and has been shown to significantly improve clinical outcomes for patients with HER2-positive metastatic breast cancer (MBC) compared to trastuzumab plus chemotherapy alone. Pertuzumab is a humanized monoclonal antibody that binds to the extracellular portion of the receptor on a domain distinct from the binding site of trastuzumab. More recently, two additional HER2-directed therapies have been approved for HER2-positive breast cancer. While trastuzumab and lapatinib had been the mainstays of treatment in combination with chemotherapy, innate and acquired resistance to these therapies occur. Policy of Dealing with Allegations of Research MisconductĪbstract: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have revolutionized the treatment of HER2-positive breast cancer, both in the metastatic and early stage settings.Policy of Screening for Plagiarism Process.
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