Expert opinion on biological therapy
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Expert Opin Biol Ther · Oct 2007
ReviewImatinib mesylate in the treatment of hematologic malignancies.
The treatment of hematologic malignancies has been based for many years on chemotherapy and possibly, for the more aggressive forms, stem cell transplantation. In 2001, the signal transduction inhibitor 571 (STI571, imatinib mesylate) was reported to have striking effects in chronic myeloid leukaemia patients. Since then, imatinib became the first molecular-targeted agent approved for the treatment of human cancer and was later on demonstrated to be effective in other malignancies, such as Philadelphia positive acute lymphoid leukemia, hypereosinophilic syndromes, gastrointestinal stromal tumours and more recently, systemic mastocytosis and other myeloprolipherative disease-carrying platelet-derived growth factor receptor abnormalities. In this article, the authors review the evidence which led to imatinib approval in the treatment of several of the above mentioned diseases.
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Expert Opin Biol Ther · Jun 2007
ReviewPotential of oligonucleotide-mediated exon-skipping therapy for Duchenne muscular dystrophy.
Many of the mutations associated with Duchenne muscular dystrophy can potentially be rescued by exon-skipping therapy, targeting selected exons of prespliced mRNA for the dystrophin gene with antisense oligonucleotides, thereby restoring reading frames. The recent development of antisense oligonucleotides with higher stability and lower toxicity, such as morpholinos, has made it possible to restore dystrophin efficiently in dystrophic mice in vivo with no obvious side effects. There seems little doubt that such exon-skipping therapy is destined to proceed to the clinical application stage in patients with Duchenne muscular dystrophy. ⋯ At present, this multi-exon skipping strategy is being investigated in dystrophic dogs as well as dystrophic mice. There are several challenges that still need to be overcome, including the low uptake of antisense oligonucleotides into the heart and the need to design efficient, nontoxic, cost-effective oligonucleotides. This review summarizes recent progress in exon-skipping therapy and discusses future perspectives with regard to human clinical trials.
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Expert Opin Biol Ther · Jun 2007
ReviewEffects of anticoagulant strategies on activation of inflammation and coagulation.
Acute inflammatory events, such as those that occur in sepsis, lead to dysregulation of the coagulation cascade. The hemostatic imbalance in sepsis, characterized by the excessive activation of procoagulant pathways and the impairment of anticoagulant activity, leads to disseminated intravascular coagulation and results in microvascular thrombosis, tissue hypoperfusion and, ultimately, multiple organ failure and death. ⋯ This review summarizes the available experimental and clinical data regarding the interaction between coagulation and inflammation, focusing on the two anticoagulants which are in clinical use, antithrombin and activated protein C. Identification of the different biological mechanisms of the two endogenous anticoagulants might help to determine target patient populations as well as to develop new anticoagulant analogs that differ in there respective effects in coagulation and inflammation.
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Expert Opin Biol Ther · Apr 2007
ReviewAdjuvant treatment of breast cancer: impact of monoclonal antibody therapy directed against the HER2 receptor.
The use of chemotherapy and endocrine therapies as adjuncts to the treatment of early-stage breast cancer has yielded small but significant improvements in disease-free and overall survival. Increased understanding of the role of growth factor receptors enabled the rational development of agents that are capable of modulating their function. ⋯ As a consequence, trastuzumab has been tested in the adjuvant setting the results of which have been presented recently. This review briefly summarises the use of trastuzumab in advanced breast cancer and describes recent studies of its use in the adjuvant setting.
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Cetuximab is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor and thereby inhibits cell proliferation, metastasis and angiogenesis. Preclinical studies indicate that cetuximab induces synergistic antitumor activity when combined with chemotherapy or radiation. This observation is supported by clinical trials demonstrating that cetuximab improves tumor response when used in conjunction with modern chemotherapy in patients with metastatic colorectal cancer. ⋯ In pretreated patients, cetuximab may restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Ongoing studies are investigating the integration of anti-epidermal growth factor receptor and anti-vascular endothelial growth factor strategies into new treatment regimens. Promising results have already been obtained in a trial combining irinotecan, bevacizumab and cetuximab.