Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anticancer drugs have been explored by means of random screening and demonstrated to be active against not only hematologic malignancies but also some solid tumors. Recent progress in the field of molecular biology has identified many new molecular targets for anticancer drugs. In this review, for example, signal-transduction pathways, which are influenced by newer agents like the taxanes (paclitaxel [Taxol] and docetaxel [Taxotere]) and the protein kinase C activator gnidimacrin, are evaluated. Efforts under way to integrate these new compounds into clinical trials are discussed.
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PMID:Overcoming drug resistance in lung cancer. 951 19

With best supportive care alone, patients with metastatic non-small-cell lung cancer (NSCLC) have a median survival of 4 to 5 months and a 1-year survival rate of approximately 10%. Trials carried out in the 1980s and 1990s comparing chemotherapy to best supportive care reported variable efficacy results; however, a pivotal meta-analysis of these data indicated that cisplatin-based chemotherapy provided a survival benefit in advanced NSCLC. In the past decade newer agents such as gemcitabine (Gemzar), vinorelbine, paclitaxel, and docetaxel (Taxotere) have all demonstrated activity in NSCLC as single agents; consequently these agents have been combined with cisplatin or carboplatin. Randomized phase III trials comparing these "newer" platin-based doublets have failed to identify an optimal platinum-based doublet therapy regimen. Though it is clear that chemotherapy is an appropriate treatment for many patients with lung cancer, there a sense in which the use of traditional chemotherapeutic agents has reached a therapeutic plateau. Increased understanding of cancer biology has revealed numerous potential therapeutic strategies, including targeting the epidermal growth factor receptor, protein kinase C, rexinoid receptors, and the angiogenesis pathway. The Eastern Cooperative Oncology Group study E4599 comparing paclitaxel/carboplatin with/without bevacizumab is the first phase III randomized trial to show a survival advantage with the addition of a molecularly targeted agent to chemotherapy in the chemotherapy-naive patient population. Future studies will involve the evaluation of additional targeted agents plus chemotherapy as well as looking at combinations of these targeted agents alone or with chemotherapy.
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PMID:First-line treatment for advanced non-small-cell lung cancer. 1642 20

Our previous studies revealed that Docetaxel-induced apoptosis of melanoma cells is entirely dependent on activation of the JNK signalling pathway. Here, we show that Docetaxel-induced apoptosis is mediated by induction of ER stress. This was shown by Docetaxel-induced activation of proteins involved in ER stress signalling namely GRP78, ATF6, IRE1alpha, and PERK/eIF2alpha. Knockdown of IRE1alpha by siRNA markedly inhibited Docetaxel-induced JNK activation and downstream targets of JNK indicating that activation of IRE1alpha was upstream of activation of the JNK. Co-immunoprecipitation experiments showed that activation of JNK is due to activation of ASK1 through formation of an IRE1alpha-TRAF2-ASK1 complex. ER stress mediated activation of the JNK pathway is downstream of activation of PKCdelta in that downregulation of PKCdelta expression using specific PKCdelta siRNA significantly inhibited Docetaxel-induced activation of IRE1alpha and the JNK pathway. These findings provide new insights to understand the mode of action of taxanes in treatment of human melanoma.
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PMID:Involvement of endoplasmic reticulum stress in Docetaxel-induced JNK-dependent apoptosis of human melanoma. 1898 85