A case study of personalized therapy for osteosarcoma
Background Effective targeted therapies are needed in sarcomas, but the biological heterogeneity of these tumors has presented a challenge to clinical integration of small molecule inhibitors in sarcoma treatment. Here we outline a process to personalize therapy for sarcomas through a case study of...
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| Veröffentlicht in: | Pediatric blood & cancer 2013-08, Vol.60 (8), p.1313-1319 |
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| creator | Davis, Lara E. Hofmann, Nicolle E. Li, Guangheng Huang, Elaine T. Loriaux, Marc M. Bracha, Shay Helfand, Stuart C. Mata, John E. Marley, Kevin Mansoor, Atiya Tyner, Jeffrey W. Abraham, Jinu Séguin, Bernard Keller, Charles |
| description | Background
Effective targeted therapies are needed in sarcomas, but the biological heterogeneity of these tumors has presented a challenge to clinical integration of small molecule inhibitors in sarcoma treatment. Here we outline a process to personalize therapy for sarcomas through a case study of a canine with spontaneous osteosarcoma.
Procedure
Rapid establishment of a primary tumor cell culture is described, followed by efficient functional characterization of the tumor that identified the Src inhibitor dasatinib as the most effective targeted therapy for this individual dog.
Results
Adjuvant dasatinib was administered for a total of 26 weeks following treatment with chemotherapy. Pharmacokinetic studies confirm that a therapeutic serum concentration was achieved at a tolerable dose of 0.75 mg/kg/day. The canine patient remains without evidence of recurrent disease 24 months following initial diagnosis.
Conclusions
The approach described through this illustrative case study is broadly applicable and might be used for other solid tumors in canines as well as in humans. Pediatr Blood Cancer 2013;60:1313–1319. © 2013 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/pbc.24512 |
| format | Article |
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Effective targeted therapies are needed in sarcomas, but the biological heterogeneity of these tumors has presented a challenge to clinical integration of small molecule inhibitors in sarcoma treatment. Here we outline a process to personalize therapy for sarcomas through a case study of a canine with spontaneous osteosarcoma.
Procedure
Rapid establishment of a primary tumor cell culture is described, followed by efficient functional characterization of the tumor that identified the Src inhibitor dasatinib as the most effective targeted therapy for this individual dog.
Results
Adjuvant dasatinib was administered for a total of 26 weeks following treatment with chemotherapy. Pharmacokinetic studies confirm that a therapeutic serum concentration was achieved at a tolerable dose of 0.75 mg/kg/day. The canine patient remains without evidence of recurrent disease 24 months following initial diagnosis.
Conclusions
The approach described through this illustrative case study is broadly applicable and might be used for other solid tumors in canines as well as in humans. Pediatr Blood Cancer 2013;60:1313–1319. © 2013 Wiley Periodicals, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.24512</identifier><identifier>PMID: 23526721</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Bone Neoplasms - diagnostic imaging ; Bone Neoplasms - drug therapy ; Bone Neoplasms - veterinary ; canine ; Cell Line, Tumor ; Dasatinib ; Dog Diseases - diagnostic imaging ; Dog Diseases - drug therapy ; Dogs ; Hematology ; Oncology ; osteosarcoma ; Osteosarcoma - diagnostic imaging ; Osteosarcoma - drug therapy ; Osteosarcoma - veterinary ; Pediatrics ; Protein Kinase Inhibitors - administration & dosage ; Protein Kinase Inhibitors - pharmacokinetics ; Pyrimidines - administration & dosage ; Pyrimidines - pharmacokinetics ; Radiography ; src-Family Kinases - antagonists & inhibitors ; Thiazoles - administration & dosage ; Thiazoles - pharmacokinetics ; Time Factors ; tyrosine kinase inhibitor</subject><ispartof>Pediatric blood & cancer, 2013-08, Vol.60 (8), p.1313-1319</ispartof><rights>Copyright © 2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3912-31ad03bf190b4e3fb339e45b0ca6c5d01c307b00856e45ecc186b51b2f497cb73</citedby><cites>FETCH-LOGICAL-c3912-31ad03bf190b4e3fb339e45b0ca6c5d01c307b00856e45ecc186b51b2f497cb73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.24512$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.24512$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23526721$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Davis, Lara E.</creatorcontrib><creatorcontrib>Hofmann, Nicolle E.</creatorcontrib><creatorcontrib>Li, Guangheng</creatorcontrib><creatorcontrib>Huang, Elaine T.</creatorcontrib><creatorcontrib>Loriaux, Marc M.</creatorcontrib><creatorcontrib>Bracha, Shay</creatorcontrib><creatorcontrib>Helfand, Stuart C.</creatorcontrib><creatorcontrib>Mata, John E.</creatorcontrib><creatorcontrib>Marley, Kevin</creatorcontrib><creatorcontrib>Mansoor, Atiya</creatorcontrib><creatorcontrib>Tyner, Jeffrey W.</creatorcontrib><creatorcontrib>Abraham, Jinu</creatorcontrib><creatorcontrib>Séguin, Bernard</creatorcontrib><creatorcontrib>Keller, Charles</creatorcontrib><title>A case study of personalized therapy for osteosarcoma</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
Effective targeted therapies are needed in sarcomas, but the biological heterogeneity of these tumors has presented a challenge to clinical integration of small molecule inhibitors in sarcoma treatment. Here we outline a process to personalize therapy for sarcomas through a case study of a canine with spontaneous osteosarcoma.
Procedure
Rapid establishment of a primary tumor cell culture is described, followed by efficient functional characterization of the tumor that identified the Src inhibitor dasatinib as the most effective targeted therapy for this individual dog.
Results
Adjuvant dasatinib was administered for a total of 26 weeks following treatment with chemotherapy. Pharmacokinetic studies confirm that a therapeutic serum concentration was achieved at a tolerable dose of 0.75 mg/kg/day. The canine patient remains without evidence of recurrent disease 24 months following initial diagnosis.
Conclusions
The approach described through this illustrative case study is broadly applicable and might be used for other solid tumors in canines as well as in humans. Pediatr Blood Cancer 2013;60:1313–1319. © 2013 Wiley Periodicals, Inc.</description><subject>Animals</subject><subject>Bone Neoplasms - diagnostic imaging</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Bone Neoplasms - veterinary</subject><subject>canine</subject><subject>Cell Line, Tumor</subject><subject>Dasatinib</subject><subject>Dog Diseases - diagnostic imaging</subject><subject>Dog Diseases - drug therapy</subject><subject>Dogs</subject><subject>Hematology</subject><subject>Oncology</subject><subject>osteosarcoma</subject><subject>Osteosarcoma - diagnostic imaging</subject><subject>Osteosarcoma - drug therapy</subject><subject>Osteosarcoma - veterinary</subject><subject>Pediatrics</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Protein Kinase Inhibitors - pharmacokinetics</subject><subject>Pyrimidines - administration & dosage</subject><subject>Pyrimidines - pharmacokinetics</subject><subject>Radiography</subject><subject>src-Family Kinases - antagonists & inhibitors</subject><subject>Thiazoles - administration & dosage</subject><subject>Thiazoles - pharmacokinetics</subject><subject>Time Factors</subject><subject>tyrosine kinase inhibitor</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E1PwyAYB3BiNM63g1_ANPGih04eKKU9zkXny6IeNHojQGns7EaFNjo_vWh1BxNPEPJ7_uH5I7QPeAgYk5NG6SFJGJA1tAUsYTHDwNdXd5wP0Lb3s0BTzLJNNCCUkZQT2EJsFGnpTeTbrlhGtowa47xdyLr6MEXUPhsnm2VUWhdZ3xrrpdN2LnfRRilrb_Z-zh30cH52P76Ip7eTy_FoGmuaA4kpyAJTVUKOVWJoqSjNTcIU1jLVrMCgKeYK44yl4dloDVmqGChSJjnXitMddNTnNs6-dsa3Yl55bepaLoztvACa8ixLCKSBHv6hM9u5sEivAEMCSVDHvdLOeu9MKRpXzaVbCsDiq0sRuhTfXQZ78JPYqbkpVvK3vABOevBW1Wb5f5K4Ox3_Rsb9RBXKfF9NSPciUk45E483EzF9uiLkmufh35_Wg4pB</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Davis, Lara E.</creator><creator>Hofmann, Nicolle E.</creator><creator>Li, Guangheng</creator><creator>Huang, Elaine T.</creator><creator>Loriaux, Marc M.</creator><creator>Bracha, Shay</creator><creator>Helfand, Stuart C.</creator><creator>Mata, John E.</creator><creator>Marley, Kevin</creator><creator>Mansoor, Atiya</creator><creator>Tyner, Jeffrey W.</creator><creator>Abraham, Jinu</creator><creator>Séguin, Bernard</creator><creator>Keller, Charles</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201308</creationdate><title>A case study of personalized therapy for osteosarcoma</title><author>Davis, Lara E. ; Hofmann, Nicolle E. ; Li, Guangheng ; Huang, Elaine T. ; Loriaux, Marc M. ; Bracha, Shay ; Helfand, Stuart C. ; Mata, John E. ; Marley, Kevin ; Mansoor, Atiya ; Tyner, Jeffrey W. ; Abraham, Jinu ; Séguin, Bernard ; Keller, Charles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3912-31ad03bf190b4e3fb339e45b0ca6c5d01c307b00856e45ecc186b51b2f497cb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Bone Neoplasms - diagnostic imaging</topic><topic>Bone Neoplasms - drug therapy</topic><topic>Bone Neoplasms - veterinary</topic><topic>canine</topic><topic>Cell Line, Tumor</topic><topic>Dasatinib</topic><topic>Dog Diseases - diagnostic imaging</topic><topic>Dog Diseases - drug therapy</topic><topic>Dogs</topic><topic>Hematology</topic><topic>Oncology</topic><topic>osteosarcoma</topic><topic>Osteosarcoma - diagnostic imaging</topic><topic>Osteosarcoma - drug therapy</topic><topic>Osteosarcoma - veterinary</topic><topic>Pediatrics</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Protein Kinase Inhibitors - pharmacokinetics</topic><topic>Pyrimidines - administration & dosage</topic><topic>Pyrimidines - pharmacokinetics</topic><topic>Radiography</topic><topic>src-Family Kinases - antagonists & inhibitors</topic><topic>Thiazoles - administration & dosage</topic><topic>Thiazoles - pharmacokinetics</topic><topic>Time Factors</topic><topic>tyrosine kinase inhibitor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Davis, Lara E.</creatorcontrib><creatorcontrib>Hofmann, Nicolle E.</creatorcontrib><creatorcontrib>Li, Guangheng</creatorcontrib><creatorcontrib>Huang, Elaine T.</creatorcontrib><creatorcontrib>Loriaux, Marc M.</creatorcontrib><creatorcontrib>Bracha, Shay</creatorcontrib><creatorcontrib>Helfand, Stuart C.</creatorcontrib><creatorcontrib>Mata, John E.</creatorcontrib><creatorcontrib>Marley, Kevin</creatorcontrib><creatorcontrib>Mansoor, Atiya</creatorcontrib><creatorcontrib>Tyner, Jeffrey W.</creatorcontrib><creatorcontrib>Abraham, Jinu</creatorcontrib><creatorcontrib>Séguin, Bernard</creatorcontrib><creatorcontrib>Keller, Charles</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Davis, Lara E.</au><au>Hofmann, Nicolle E.</au><au>Li, Guangheng</au><au>Huang, Elaine T.</au><au>Loriaux, Marc M.</au><au>Bracha, Shay</au><au>Helfand, Stuart C.</au><au>Mata, John E.</au><au>Marley, Kevin</au><au>Mansoor, Atiya</au><au>Tyner, Jeffrey W.</au><au>Abraham, Jinu</au><au>Séguin, Bernard</au><au>Keller, Charles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A case study of personalized therapy for osteosarcoma</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2013-08</date><risdate>2013</risdate><volume>60</volume><issue>8</issue><spage>1313</spage><epage>1319</epage><pages>1313-1319</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
Effective targeted therapies are needed in sarcomas, but the biological heterogeneity of these tumors has presented a challenge to clinical integration of small molecule inhibitors in sarcoma treatment. Here we outline a process to personalize therapy for sarcomas through a case study of a canine with spontaneous osteosarcoma.
Procedure
Rapid establishment of a primary tumor cell culture is described, followed by efficient functional characterization of the tumor that identified the Src inhibitor dasatinib as the most effective targeted therapy for this individual dog.
Results
Adjuvant dasatinib was administered for a total of 26 weeks following treatment with chemotherapy. Pharmacokinetic studies confirm that a therapeutic serum concentration was achieved at a tolerable dose of 0.75 mg/kg/day. The canine patient remains without evidence of recurrent disease 24 months following initial diagnosis.
Conclusions
The approach described through this illustrative case study is broadly applicable and might be used for other solid tumors in canines as well as in humans. Pediatr Blood Cancer 2013;60:1313–1319. © 2013 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23526721</pmid><doi>10.1002/pbc.24512</doi><tpages>7</tpages></addata></record> |
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| subjects | Animals Bone Neoplasms - diagnostic imaging Bone Neoplasms - drug therapy Bone Neoplasms - veterinary canine Cell Line, Tumor Dasatinib Dog Diseases - diagnostic imaging Dog Diseases - drug therapy Dogs Hematology Oncology osteosarcoma Osteosarcoma - diagnostic imaging Osteosarcoma - drug therapy Osteosarcoma - veterinary Pediatrics Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - pharmacokinetics Pyrimidines - administration & dosage Pyrimidines - pharmacokinetics Radiography src-Family Kinases - antagonists & inhibitors Thiazoles - administration & dosage Thiazoles - pharmacokinetics Time Factors tyrosine kinase inhibitor |
| title | A case study of personalized therapy for osteosarcoma |
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