In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy
The E1B-deleted, replication-competent ONYX-015 (dl1520) adenovirus was originally described as being able to selectively kill p53-deficient cells due to a requirement of p53 inactivation for efficient viral replication. This hypothesis has become controversial because subsequent in vitro studies ha...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2000-03, Vol.60 (5), p.1193-1196 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | ROGULSKI, K. R FREYTAG, S. O KANG ZHANG GILBERT, J. D PAIELLI, D. L JAE HO KIM HEISE, C. C KIRN, D. H |
| description | The E1B-deleted, replication-competent ONYX-015 (dl1520) adenovirus was originally described as being able to selectively kill p53-deficient cells due to a requirement of p53 inactivation for efficient viral replication. This hypothesis has become controversial because subsequent in vitro studies have demonstrated that the host range specificity of ONYX-015 is independent of p53 gene status. Using a pair of isogenic cell lines that differ only in their p53 status, we demonstrate here that although ONYX-015 can replicate in both p53 wild-type and mutant cells in vitro, the virus demonstrates significantly greater antitumor activity against mutant p53 tumors in vivo. Moreover, ONYX-015 viral therapy can be combined with radiation to improve tumor control beyond that of either monotherapy. The results demonstrate that ONYX-015 can discern in vivo between tumors having a different p53 status and that it may be an effective neoadjuvant to radiation therapy. |
| format | Article |
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Moreover, ONYX-015 viral therapy can be combined with radiation to improve tumor control beyond that of either monotherapy. The results demonstrate that ONYX-015 can discern in vivo between tumors having a different p53 status and that it may be an effective neoadjuvant to radiation therapy.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 10728673</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>adeno-associated virus ; Adenoviridae ; Antineoplastic agents ; Biological and medical sciences ; Drug Resistance, Neoplasm - genetics ; Gene Expression Regulation, Neoplastic ; General aspects ; Genes, p53 ; Humans ; Medical sciences ; Mutation ; Neoadjuvant Therapy ; Neoplasms - genetics ; Neoplasms - radiotherapy ; Neoplasms - therapy ; ONYX-015 ; Pharmacology. Drug treatments ; Tumor Cells, Cultured</subject><ispartof>Cancer research (Chicago, Ill.), 2000-03, Vol.60 (5), p.1193-1196</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1361098$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10728673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ROGULSKI, K. R</creatorcontrib><creatorcontrib>FREYTAG, S. O</creatorcontrib><creatorcontrib>KANG ZHANG</creatorcontrib><creatorcontrib>GILBERT, J. D</creatorcontrib><creatorcontrib>PAIELLI, D. L</creatorcontrib><creatorcontrib>JAE HO KIM</creatorcontrib><creatorcontrib>HEISE, C. C</creatorcontrib><creatorcontrib>KIRN, D. H</creatorcontrib><title>In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The E1B-deleted, replication-competent ONYX-015 (dl1520) adenovirus was originally described as being able to selectively kill p53-deficient cells due to a requirement of p53 inactivation for efficient viral replication. This hypothesis has become controversial because subsequent in vitro studies have demonstrated that the host range specificity of ONYX-015 is independent of p53 gene status. Using a pair of isogenic cell lines that differ only in their p53 status, we demonstrate here that although ONYX-015 can replicate in both p53 wild-type and mutant cells in vitro, the virus demonstrates significantly greater antitumor activity against mutant p53 tumors in vivo. Moreover, ONYX-015 viral therapy can be combined with radiation to improve tumor control beyond that of either monotherapy. The results demonstrate that ONYX-015 can discern in vivo between tumors having a different p53 status and that it may be an effective neoadjuvant to radiation therapy.</description><subject>adeno-associated virus</subject><subject>Adenoviridae</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>General aspects</subject><subject>Genes, p53</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Neoadjuvant Therapy</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - radiotherapy</subject><subject>Neoplasms - therapy</subject><subject>ONYX-015</subject><subject>Pharmacology. Drug treatments</subject><subject>Tumor Cells, Cultured</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0EtLAzEQB_Agiq3VryA5iLeFZPM-SvFRKPaioKdlssnayD7qJlvYb-9KKx49DMPw_80c5gTNqWA6U5yLUzQnhOhMcJXP0EWMn9MoKBHnaEaJyrVUbI7KVYv3Yd9haFNIQ9P1GMoU9iGNuKvw5vn9LSNU4BBxaKt68G3pHbYj3gmGY4I0xGnV_eQwfDS-TYe4Bxe6tPU97MZLdFZBHf3VsS_Q68P9y_IpW28eV8u7dbZlhKQMLCOgpbRCaumtMNYQDVNZ6bnSmlnLmGXAuAGwqswpd-BcrommLqeSLdDt4e6u774GH1PRhFj6uobWd0MsFDFGcaP-hVRNT-OGTPD6CAfbeFfs-tBAPxa__5vAzRFALKGuemjLEP8ck5QYzb4BdsB4nw</recordid><startdate>20000301</startdate><enddate>20000301</enddate><creator>ROGULSKI, K. R</creator><creator>FREYTAG, S. O</creator><creator>KANG ZHANG</creator><creator>GILBERT, J. D</creator><creator>PAIELLI, D. L</creator><creator>JAE HO KIM</creator><creator>HEISE, C. C</creator><creator>KIRN, D. 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H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h300t-ab30a866b5686eb59b908a908b6e47883bb33b3a349aab7c214dadd28081d2163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>adeno-associated virus</topic><topic>Adenoviridae</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>General aspects</topic><topic>Genes, p53</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Neoadjuvant Therapy</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - radiotherapy</topic><topic>Neoplasms - therapy</topic><topic>ONYX-015</topic><topic>Pharmacology. Drug treatments</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ROGULSKI, K. R</creatorcontrib><creatorcontrib>FREYTAG, S. O</creatorcontrib><creatorcontrib>KANG ZHANG</creatorcontrib><creatorcontrib>GILBERT, J. D</creatorcontrib><creatorcontrib>PAIELLI, D. L</creatorcontrib><creatorcontrib>JAE HO KIM</creatorcontrib><creatorcontrib>HEISE, C. C</creatorcontrib><creatorcontrib>KIRN, D. 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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | adeno-associated virus Adenoviridae Antineoplastic agents Biological and medical sciences Drug Resistance, Neoplasm - genetics Gene Expression Regulation, Neoplastic General aspects Genes, p53 Humans Medical sciences Mutation Neoadjuvant Therapy Neoplasms - genetics Neoplasms - radiotherapy Neoplasms - therapy ONYX-015 Pharmacology. Drug treatments Tumor Cells, Cultured |
| title | In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy |
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