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These are exciting days for physicians treating patients with Lymphoma. The introduction of chemotherapy has resulted in dramatic improvement of outcome in the early 1970s, when the diagnosis of leukaemia or lymphoma meant a death warrant in the vast majority of cases. However, variation of chemotherapeutic components and increasing the dose during the following decades of research has only resulted in small additional benefits - a notable exception is Hodgkin 's disease which can be cured by aggressive polychemotherapy regimens in most cases. Therefore, chemotherapy regimens of the early days like CHOP still remained the gold standard for lymphoma therapy at the beginning of this century. The same was true for many other haematological diseases with very view improvements, if any, in terms of survival for most patients. Beginning with the success story of the tyrosine kinase inhibitor Imatinib in CML, strong efforts have been made to treat haematological malignancies with more specific drugs which are directed against cell surface molecules, signal transduction pathways or the cell cycle. This special issue of current drug targets, entitled “Beyond chemotherapy: future directions in lymphoma treatment” contains reviews dealing with very exciting fields of clinical and preclinical research in the field of targeted therapy in malignant lymphoma. The issue starts with a review in which the current status of radioimmunotherapy is presented by Bruce Cheson. Another approach to enhance cytotoxic activity of monoclonal antibodies is to add a plant or bacteria toxin - available data are summarized in the following paper by Kreitman and Pastan. The next review by Winkler et al, nicely illustrates the interplay of genetics, gene expression and targeted therapy using B-CLL as a prototype disease. Like BCR-ABL in CML, NPM-ALK is an oncogenic tyrosine kinase which is involved in lymphomagenesis. The review of Miething and colleagues describes the efforts to better understand and finally target this oncogenic event. The BCL-10/MALT- 1 pathway is another signal transduction pathway which is involved in lymphomagenesis and might be a promising drug target as reviewed by Jost and coworkers. A real success story of targeted therapy is described by Mitsiades et al. Proteasome inhibition has already been shown to be a very effective treatment approach in multiple myeloma and is just being tested in lymphoma treatment as well. In contrast to cytotoxic chemotherapy, drugs targeting the cell cycle might be able to stop disease progression or maintain remissions for prolonged periods of time. Ringshausen and coworkers present preclinical and clinical data currently available. Another promising approach is to modulate pro- and antiapoptotic mechanisms in cancer and lymphoma as reviewed by Meiler and Schuler. Last but not least, considerable progress has been made in bringing immnotherapeutic approaches from bench to bedside. Different strategies including active and passive immunotherapy are reviewed by Kofler and colleagues at the end of this issue. Taken together, these nine reviews present current research dealing with new drug targets in lymphoma treatment. Some of the therapeutic approaches presented in this issue will likely alter the way we treat lymphoma in the future.
TU Munchen IIIrd Departement of Medicine Ismaninger Str.22 81675 Munchen Germany.
Publication date: October 1, 2006
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Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.