Discovery and development of anticancer aptamers. Export

@article{citeulike:5376475, abstract = {Aptamers, also termed as decoys or "chemical antibodies," represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific tight binding to protein targets. In some cases and as opposed to antisense oligonucleotides, effects can be mediated against extracellular targets, thereby preventing a need for intracellular transportation. The first aptamer approved for use in man is a RNA-based molecule (Macugen, pegaptanib) that is administered locally (intravitreally) to treat age-related macular degeneration by targeting vascular endothelial growth factor. The most advanced aptamer in the cancer setting is AS1411, formerly known as AGRO100, which is being administered systemically in clinical trials. AS1411 is a 26-mer unmodified guanosine-rich oligonucleotide, which induces growth inhibition in vitro, and has shown activity against human tumor xenografts in vivo. The mechanism underlying its antiproliferative effects in cancer cells seems to involve initial binding to cell surface nucleolin and internalization, leading to an inhibition of DNA replication. In contrast to other unmodified oligonucleotides, AS1411 is relatively stable in serum-containing medium, probably as a result of the formation of dimers and a quartet structure. In a dose escalation phase I study in patients with advanced solid tumors, doses up to 10 mg/kg/d (using a four or seven continuous infusion regime) have been studied. Promising signs of activity have been reported (multiple cases of stable disease and one near complete response in a patient with renal cancer) in the absence of any significant adverse effects. Further trials are ongoing in renal and non-small cell lung cancers. In preclinical studies, additional aptamers have been described against several cancer targets, such as tenascin-C, the transcription factor signal transducer and activator of transcription 3, and antiapoptotic and Ku proteins.}, author = {Ireson, Christopher R. and Kelland, Lloyd R.}, citeulike-article-id = {5376475}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1535-7163.MCT-06-0172}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17172400}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17172400}, doi = {10.1158/1535-7163.MCT-06-0172}, issn = {1535-7163}, journal = {Molecular cancer therapeutics}, keywords = {aptamer}, month = {December}, number = {12}, pages = {2957--2962}, posted-at = {2009-08-06 05:09:47}, priority = {2}, title = {Discovery and development of anticancer aptamers.}, url = {http://dx.doi.org/10.1158/1535-7163.MCT-06-0172}, volume = {5}, year = {2006} }

TY - JOUR ID - citeulike:5376475 L3 - citeulike-article-id:5376475 N2 - Aptamers, also termed as decoys or "chemical antibodies," represent an emerging class of therapeutics. They are short DNA or RNA oligonucleotides or peptides that assume a specific and stable three-dimensional shape in vivo, thereby providing specific tight binding to protein targets. In some cases and as opposed to antisense oligonucleotides, effects can be mediated against extracellular targets, thereby preventing a need for intracellular transportation. The first aptamer approved for use in man is a RNA-based molecule (Macugen, pegaptanib) that is administered locally (intravitreally) to treat age-related macular degeneration by targeting vascular endothelial growth factor. The most advanced aptamer in the cancer setting is AS1411, formerly known as AGRO100, which is being administered systemically in clinical trials. AS1411 is a 26-mer unmodified guanosine-rich oligonucleotide, which induces growth inhibition in vitro, and has shown activity against human tumor xenografts in vivo. The mechanism underlying its antiproliferative effects in cancer cells seems to involve initial binding to cell surface nucleolin and internalization, leading to an inhibition of DNA replication. In contrast to other unmodified oligonucleotides, AS1411 is relatively stable in serum-containing medium, probably as a result of the formation of dimers and a quartet structure. In a dose escalation phase I study in patients with advanced solid tumors, doses up to 10 mg/kg/d (using a four or seven continuous infusion regime) have been studied. Promising signs of activity have been reported (multiple cases of stable disease and one near complete response in a patient with renal cancer) in the absence of any significant adverse effects. Further trials are ongoing in renal and non-small cell lung cancers. In preclinical studies, additional aptamers have been described against several cancer targets, such as tenascin-C, the transcription factor signal transducer and activator of transcription 3, and antiapoptotic and Ku proteins. IS - 12 JF - Molecular cancer therapeutics SN - 1535-7163 EP - 2962 TI - Discovery and development of anticancer aptamers. VL - 5 SP - 2957 KW - aptamer AU - Ireson, Christopher AU - Kelland, Lloyd PY - 2006/12// UR - http://dx.doi.org/10.1158/1535-7163.MCT-06-0172 ER -