Current cancer drug targets
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Curr Cancer Drug Targets · Mar 2006
ReviewLiposomal muramyl tripeptide phosphatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma.
About one third of osteosarcoma patients develop lung metastasis refractory to chemotherapy. Recent studies indicate that biological response modifiers activating the patient's immune system may help controlling minimal residual disease via pathways distinct from those used by cytotoxic drugs, and therefore prove effective against tumor resistance. Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic lipophilic glycopeptide capable of activating monocytes and macrophages to a tumoricidal state. ⋯ In early trials, most side effects of L-MTP-PE were minimal. L-MTP-PE showed signs of efficacy in treatment of patients with recurrent osteosarcoma and the encouraging results from phase II studies led to a phase III trial conducted by the Children's Oncology Group in patients with newly diagnosed high-grade osteosarcoma. Patients were treated with or without L-MTP-PE in combination with multi-drug chemotherapy in adjuvant setting; significantly higher overall survival and disease-free survival were observed in the group receiving L-MTP-PE.
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Curr Cancer Drug Targets · Jun 2002
ReviewPharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan.
Topotecan and irinotecan (CPT-11) are both anticancer agents active in the inhibition of topoisomerase I, an enzyme involved in DNA replication and RNA transcription. During the last decades, an immense amount of research into this class of anticancer agents has been conducted, the positive results of which led to the clinical use of topotecan and CPT-11 in ovarian cancer and colorectal cancer, respectively. Here, we review the currently most important pharmacologic aspects of these drugs, including their mechanisms of action, metabolism, activity- and toxicity-profiles and mechanisms of resistance, to provide a global insight into their pharmacology. ⋯ Pharmacokinetic and pharmacodynamic biomodulation, to enhance the bioavailability of the active anticancer agent or to reduce drug related toxicities have currently reached clinical application. As pharmacogenetics enters the clinical stage, this will lead to more "fine-tuning" in anticancer treatment (for instance by individualized dosing). The clarification of the mechanisms of action and resistance of topotecan and CPT-11 should enable us to understand their pharmacological behavior even better and might lead to the development of more potent camptothecin-derivatives in the future.
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Curr Cancer Drug Targets · May 2001
ReviewThe role of the tyrosine kinase inhibitor STI571 in the treatment of cancer.
The tyrosine kinase inhibitor STI571 exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of cancer. This review details the steps in the development of this agent and highlights why this drug has been so successful in the treatment of chronic myelogenous leukaemia. Future directions including the mechanisms and management of resistance and new therapeutic strategies are discussed. Finally, the literature supporting the use of STI571 in other malignancies, including solid tumors is briefly reviewed.