Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antisense technology has emerged as an exciting and promising strategy of cancer therapy. The principle of this technology is the sequence-specific binding of an antisense oligonucleotide to target mRNA, resulting in the prevention of gene translation. The specificity of hybridization by Watson-Crick base pairing make antisense oligonucleotides attractive as tools for targeted validation and functionalization, and as therapeutics to selectively modulate the expression of genes involved in the pathogenesis of malignancies and other genetic diseases. A variety of genes known to be key regulators of apoptosis, cell growth, metastasis, and angiogenesis which are associated with the malignant phenotype of cancer cells rather than with normal cell physiology, have been validated as molecular targets for antisense therapy. One antisense compound has been approved for local treatment of cytomegalovirus-induced retinitis, and several others are in clinical trials, including those targeting the mRNA of Bcl-2, protein kinase C-alpha (PKC-alpha), c-raf or Ha-ras. In this review, we focus on the mechanism of action of antisense oligonucleotides and new technical developments, look at new targets provided by coordinated functional genomics and proteomics initiatives and summarize the most promising clinical data.
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PMID:Antisense oligonucleotides for cancer therapy-an overview. 1286 66

Preclinical and clinical studies indicate a role for AS ODNs (antisense oligonucleotides) as therapeutics for malignant diseases. The principle of antisense technology is the sequence-specific binding of an AS ODN to the target mRNA, resulting in a translational arrest. The specificity of hybridization makes antisense strategy attractive to selectively modulate the expression of genes involved in the pathogenesis of malignant diseases. One antisense drug has been approved for local therapy of CMV (cytomegalovirus) retinitis, and a number of AS ODNs are currently being tested in clinical trials, including AS ODN targeting Bcl-2, XIAP (X-linked inhibitor of apoptosis protein) and TGF-beta-2 (transforming growth factor beta-2). AS ODNs are well tolerated and may have therapeutic activity. In particular, an AS ODN to Bcl-2 has been tested in phase III clinical trials in chronic lymphocytic leukaemia, multiple myeloma and malignant melanoma. In this review, therapeutic concepts, clinical studies and new promising molecular targets to treat malignancies with AS ODNs are summarized.
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PMID:Antisense therapy in malignant diseases: status quo and quo vadis? 1652 47