Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trastuzumab (Herceptin) is an effective treatment in patients with HER2-overexpressing metastatic breast cancer. Risk of trastuzumab-induced cardiotoxicity raises concerns regarding combined use with anthracyclines or other potentially cardiotoxic agents following anthracycline treatment. We characterized interactions between trastuzumab and gemcitabine (Gemzar) and the combination of gemcitabine and cisplatin or carboplatin (Paraplatin) as such combinations might help reduce the risk of cardiotoxicity. Multiple drug effect/combination index isobologram analysis was used to study the efficacy of chemotherapeutic drug plus trastuzumab combinations in HER2-overexpressing breast cancer cell lines. Combination index values were derived from parameters of the median effect plots, and statistical tests were used to determine whether the mean combination index at multiple effect levels significantly differed from a combination index value of 1.0 (values < 1.0 indicate synergy; values > 1.0, antagonism; values equal to 1.0, additivity). At a wide range of clinically achievable drug concentrations, interactions between trastuzumab and gemcitabine were synergistic at low concentrations of gemcitabine and antagonistic at high concentrations. A consistent synergistic interaction was observed with the three-drug combination of trastuzumab plus gemcitabine plus carboplatin or cisplatin. Available clinical data on the use of trastuzumab plus gemcitabine, and trastuzumab plus gemcitabine/paclitaxel, as well as clinical data on the use of gemcitabine/cisplatin in breast cancer, are discussed. These findings indicate that trastuzumab plus gemcitabine and trastuzumab plus gemcitabine plus cisplatin or carboplatin are rational combinations to evaluate in clinical trials.
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PMID:Gemcitabine in combination with trastuzumab and/or platinum salts in breast cancer cells with HER2 overexpression. 1568 24

Cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb), together with newer chemotherapies, such as docetaxel (Taxotere; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com), paclitaxel (Taxol; Bristol-Myers Squibb), vinorelbine (Navelbine; GlaxoSmith-Kline, Philadelphia, http://www.gsk.com), pemetrexed (Alimta; Eli Lilly and Company, Indianapolis, http://www.lilly.com), and gemcitabine (Gemzar; Eli Lilly and Company), have improved treatment outcomes in both advanced non-small cell lung cancer (NSCLC) and in the adjuvant/neoadjuvant setting. Newer systemic treatments for NSCLC, used in advanced stage IV management, are beginning to be studied in earlier stages of the disease, when treatment is better tolerated and potentially curative. Hopefully, newer agents with proven efficacies in advanced disease will enhance curability. Following the successful addition of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to carboplatin/paclitaxel in advanced disease, bevacizumab is now being incorporated into adjuvant and neoadjuvant trials. Trials in stage IB-IIIA patients will study neoadjuvant docetaxel/cisplatin/bevacizumab. The discovery that patients with exon 19 and 21 mutations in the epidermal growth factor receptor gene EGFR have around an 80% response rate to gefitinib (Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE, http:// www.astrazeneca-us.com) and that this response confers survival benefit indicates its potential utility for mutation-positive patients with advanced- and earlier-stage disease. Clinical characteristics, such as never smoking status and adenocarcinoma, and especially bronchioloalveolar carcinoma histological features, can also identify individuals likely to respond to EGFR tyrosine kinase inhibitors. Studies of neoadjuvant erlotinib (Tarceva; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com) in operable NSCLC are planned. One such study includes cisplatin and docetaxel. Effective development of active agents and disease management based on molecular profiling of lung tumors will change tomorrow's standard of care.
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PMID:How today's developments in the treatment of non-small cell lung cancer will change tomorrow's standards of care. 1627 56