Expert opinion on emerging drugs
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Acute myeloid leukaemia (AML) is the most common form of leukaemia in young adults. Although 75-85% of patients will achieve complete remission after induction chemotherapy, the long-term survival is still < 50% at 5 years. Chemotherapy has increased in intensity in recent years and is perceived to have reached the limit of toxicity. ⋯ More selective delivery of chemotherapeutic agents is also feasible using humanised monoclonal antibodies, with the intriguing possibility of increasing treatment delivery without increasing the toxicity. However, despite the progress in the rational design of drugs in disorders such as chronic myeloid leukaemia, AML lacks a single specific pathognomic genetic event to act as a drug target. This review discusses the drugs presently under investigation in Phase II or Phase III trials in AML.
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Drugs that inhibit or poison the function of topoisomerase (topo) enzymes are one of the mainstays of cancer chemotherapy, and include some of the most widely used anticancer drugs. A major effort is going into improving the broad deficiencies of established agents: for topo I inhibitors, this includes better lactone stability than for camptothecin; for topo II inhibitors lower cardiotoxicity than for existing anthracycline/anthraquinone analogues and for both classes, ways to counteract cell efflux mechanisms. ⋯ This review covers 24 drugs (6 topo I inhibitors, 12 topo II inhibitors and 6 dual topo I/II inhibitors) at various stages of clinical development. Although many of the latter class are at an early stage of development, despite a lack of detailed structural biology on the target enzymes, the research area is vigorous and has the potential to open up specific new drug design approaches.
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Medical treatment of endometriosis relies on drugs that suppress ovarian steroids and induce an hypoestrogenic state that causes atrophy of ectopic endometrium. Gonadotrophin-releasing hormone (GnRH) analogues, danazol, progestogens and oestrogen-progestin combinations have all proven effective in relieving pain and reducing the extent of endometriotic implants. However, symptoms often recur after discontinuation of therapy and hypoestrogenism-related side effects limit the long-term use of most medications. ⋯ A fundamental objective of research in endometriosis treatment is to develop new therapeutic approaches based on the findings from experimental studies on the aetiopathogenesis of the disease; current research is focusing on anti-inflammatory drugs and modulators of the immune system. TNF-binding protein-1 and IL-12 have proved effective in reducing endometriotic lesions in animal models, while pentoxifylline and INF-alpha 2b have shown encouraging results in clinical studies. This area may be of paramount importance in the near future in order to develop a therapy that could prevent or eradicate endometriosis rather than merely relieving the symptoms.