Disease relevance of Tarceva

• Furthermore, inhibitors of EGFR (OSI-774 and Tyrphostin AG1478) selectively down-regulated these molecular effectors in glioblastoma cells, eliminating enhanced invasion [1].
• No severe toxicities precluded dose escalation of OSI-774 from 25 to 100 mg/d in part A [2].
• We have used matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to directly analyze protein profiles in mouse mammary tumor virus/HER2 transgenic mouse frozen tumor sections after treatment with the erbB receptor inhibitors OSI-774 and Herceptin [3].
• The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer [4].
• Erlotinib (Tarcevatrade mark, OSI-774), a potent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR), was evaluated in a phase II study to assess its activity in patients with metastatic colorectal cancer [5].

High impact information on Tarceva

• In addition, they predicted for therapeutic synergy of OSI-774 and Herceptin as well as for drug resistance [3].
• The pharmacokinetics of OSI-774 and its O-demethylated metabolite, OSI-420, were characterized [2].
• Part B patients received OSI-774 doses ranging from 50 to 200 mg given once daily for 3 weeks every 4 weeks to establish the maximum tolerated dose (MTD) [2].
• Only changes in p27 expression were related to the administered dose of OSI-774 [6].
• There was a significant decrease in phospho-EGFR (Tyr 1173) expression as determined semiquantitatively with OSI-774 treatment [2.75 +/- 0.51 (mean +/- SD) pretreatment versus 2.36 +/- 0.76 after treatment, pair comparison P = 0.01] [6].

Chemical compound and disease context of Tarceva

• Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774 [7].
• The present study examined the effects of the epidermal growth factor receptor (EGFR) inhibitor OSI-774 ("Tarceva") alone and in combination with wortmannin and/or gemcitabine on downstream signaling molecules, as well as apoptosis in primary pancreatic cancer xenografts implanted orthotopically in severely combined immunodeficient mice [8].

Biological context of Tarceva

• In preclinical studies, OSI-774 inhibited the phosphorylation of the EGFR in a dose-dependent and concentration-dependent manner resulting in cell cycle arrest and induction of apoptosis [9].
• Genomic gains and losses of genetic material in the non-transduced cell lines as assessed by comparative genomic hybridization were correlated with the IC(50) values for ART and OSI-774 and subsequently subjected to hierarchical cluster analysis and cluster image mapping [7].
• OSI-774 alone significantly inhibited phosphorylation of EGFR in both of the primary xenografts [8].
• Competitive inhibitors of adenosine triphosphate binding sites on tyrosine and serine/threonine kinases are also being evaluated in phase I/II trials; these include ZD1839, OSI-774 and CI-1033 [10].

Anatomical context of Tarceva

• In conclusion, the combination treatment of ART and OSI-774 resulted in an increased growth inhibition of GBM cell lines as compared to each drug alone [7].
• RESULTS: IC(50) values for GEO, FET, and HCT 116 cell lines exposed to OSI-774 were 12.0, 16.0, and greater than 100 mum, respectively [11].

Associations of Tarceva with other chemical compounds

• The anti-malarial artesunate (ART) and the EGFR tyrosine kinase inhibitor OSI-774 reveal profound cytotoxic activity [7].
• Some of these agents, such as ZD1839 and OSI-774, tend to bind in vitro only to the epidermal growth factor receptor tyrosine kinase while others, such as CI-1033, bind to multiple members of the ErbB family [12].
• A high-performance liquid-chromatographic (HPLC) assay with UV detection has been developed for the quantitative determination of erlotinib (OSI-774) in human plasma [13].
• Low-molecular-weight inhibitors of the EGFR tyrosine kinase also in clinical development include OSI-774, PD182905, PKI-166, CI-1033, and ZD1839 [14].
• Although wortmannin failed to enhance gemcitabine-induced apoptosis in OCIP#7 tumors, the extent of apoptosis was significantly increased with the inclusion of OSI-774 in the combination [8].

Gene context of Tarceva

• Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma [8].
• The OSI-774 induced greater (p53-independent) apoptosis in more malignant GBM phenotypes and may be a promising therapeutic agent against secondary GBM [15].

Analytical, diagnostic and therapeutic context of Tarceva

• Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models [16].
• The phase II trials will assess OSI-774 both as a single agent and in combination with existing chemotherapy regimens [347783] [17].
• Simultaneous determination of OSI-774 and its major metabolite OSI-420 in human plasma by using HPLC with UV detection [18].

References