LAKE FOREST, Calif., Oct. 10 /PRNewswire/ -- The September 2006 NDA submission of GlaxoSmithKline's Tykerb (lapatinib dytosylate), a dual inhibitor of EGFr and HEr2, highlights the immense ongoing efforts concentrated on research and development of anticancer agents that target the EGF oncogene family. According to New Medicine's Oncology KnowledgeBASE (nm|OK), Tykerb is one of more than 46 novel agents in current development that target the EGFr pathway; 2/3 of these compounds have already entered clinical trials.
The nm|OK database provides detailed, current information about developmental agents that target the many points of potential intervention along the EGFr pathway. Pharmacologic strategies include direct inhibition, novel drug delivery approaches, and vaccine strategies. Targets include the various mechanisms of EGFr activation, such as gene amplification, transcriptional abnormalities, gene mutations, and overproduction of the ligands EGF and transforming growth factor (TGF) alpha, and other downstream targets.
The first effective anti-EGFr agents included monoclonal antibodies (MAb), which bind to the extracellular domain of the receptor, and small molecule drugs, which bind to and inhibit intracellular tyrosine kinases. Other approaches include:
* synthetic nucleic sequences (including siRNA), which prevent transcription and receptor/ligand production; * gene transfer to repress transcription of receptor tyrosine kinase proteins; * EGFr/ligand-directed vaccines, which stimulate production of antibodies to enhance host immune response; and * drug delivery approaches (e.g., immunoconjugates), which target the extracellular domain of EGFr to haul cytotoxics, toxins or radioisotopes to cancer cells.
The R&D pool of anti-EGFr agents continues to grow and broaden as new mutations are discovered and more is learned about upstream and downstream effectors that modulate this pathway. Potentially important targets include molecular events related to EGFr signal transduction. The binding of EGFr ligands to the receptor, for example, activates a string of such oncogenic proteins as Ras, Raf, MEK, MAPK, among others. nm|OK includes detailed profiles of the many more novel agents that target pathways related to EGFr signal transduction.
Anti-EGFr agents are in clinical development either as monotherapies or, more commonly, in combination with approved cytotoxics, other targeted anticancer therapies, or each other. Tykerb is the latest example of a targeted anticancer drug seeking to gain approval to enter the market as a part of a combination regimen, in this case with capecitabine (Xeloda; Roche) for treatment of advanced disease.
In 2005, the four major marketed drugs targeting the EGFr pathway, trastuzumab (Herceptin; Genentech), cetuximab (Erbitux; ImClone Systems); erlotinib (Tarceva; OSI Pharmaceuticals), and the now withdrawn gefitinib (Iressa; AstraZeneca), generated worldwide sales of more than $3 billion. The recent entry of panitumumab (Vectibix; Amgen) into the USA market and the possible approval of Tykerb, create new challenges in clinical use and marketing of these agents.
About New Medicine's Oncology KnowledgeBASE (nm|OK)
New Medicine's Oncology KnowledgeBASE (nm|OK), residing at http://www.nmok.net, is an edited, inclusive analysis of all aspects of oncology drug development globally, including technologies, targets, companies, business affiliations, medical and clinical developments, including protocols and results of thousands of clinical trials, and global markets, among others. Currently, nm/OK profiles over 3,000 agents/technologies, over 1,500 targets implicated in malignancy, and over 2,000 companies developing/marketing products in the oncology sector.
Contact New Medicine for additional information or to sign up for a no-obligation demonstration of the database and a temporary 7-day pass.
New MedicineCONTACT: Katie Siafaca of New Medicine, +1-949-830-0448, fax+1-949-830-0887, info@newmedinc.com
