Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HER-2/neu oncogene, a member of the epidermal growth factor receptor or erb gene family, encodes a transmembrane tyrosine kinase receptor that has been linked to prognosis and response to therapy with the anti-HER-2-humanized monoclonal antibody, trastuzumab (Herceptin, Genentech, South San Francisco, CA) in patients with advanced metastatic breast cancer. HER-2/neu status has also been tested for its ability to predict the response of breast cancer to other therapies including hormonal therapies, topoisomerase inhibitors, and anthracyclines. This review includes an analysis of 80 published studies encompassing more than 25,000 patients designed to consider the relative advantages and disadvantages of the various methods of measuring HER-2/neu in clinical breast cancer specimens. Southern blotting, PCR amplification detection, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is reviewed along with the current studies designed to test whether HER-2/neu status can predict the response to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review will also evaluate the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response.
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PMID:Targeted therapy in breast cancer: the HER-2/neu gene and protein. 1476 15

Currently, approximately 40 drugs are registered for the chemotherapeutic treatment of cancer, the vast majority of which either interact directly with DNA (eg, alkylating, methylating, platinating agents, topoisomerase inhibitors), or affect DNA synthesis (antimetabolites). Whilst such agents remain of great importance in combination chemotherapy regimens, many cancer drug discovery groups have questioned whether any further significant gains may be made through the development of novel DNA-interactive drugs. Such agents tend to be associated with dose-limiting antiproliferative tissue toxicities (eg, myelo-suppression, nausea and vomiting, diarrhea or mucositis) which is indicative of their general lack of selectivity in targeting tumor versus normal tissue DNA. Perhaps surprisingly to some, Dr D Von Hoff (University of Texas Health Science Center, San Antonio, Texas, USA) proposed that the investigation of DNA-interactive agents is still yielding some promising agents. He illustrated this with the following new agents.
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PMID:DNA-interactive agents. 1846 68