A case study of personalized therapy for osteosarcoma
| Autor: | Bernard Séguin, Guangheng Li, Nicolle E. Hofmann, Atiya Mansoor, Shay Bracha, Charles Keller, Elaine T. Huang, Lara E. Davis, Marc M. Loriaux, Jinu Abraham, John E. Mata, Stuart C. Helfand, Kevin Marley, Jeffrey W. Tyner |
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| Rok vydání: | 2013 |
| Předmět: |
Drug
Oncology medicine.medical_specialty business.industry medicine.drug_class media_common.quotation_subject Hematology medicine.disease Response to treatment Tyrosine-kinase inhibitor Surgery Metastasis Clinical trial Dasatinib Internal medicine Pediatrics Perinatology and Child Health Medicine Osteosarcoma Personalized therapy business media_common medicine.drug |
| Zdroj: | Pediatric Blood & Cancer. 60:1313-1319 |
| ISSN: | 1545-5009 |
| DOI: | 10.1002/pbc.24512 |
| Popis: | Osteosarcomaisthemostcommonmalignantbonetumor,yettheincidenceofosteosarcomaislowenoughtoposeasignificantbarrierto the timely completion of traditionally designed clinical trials.While research laboratories continue to investigate the underlyingmechanisms of osteosarcoma, these experiments use multiply-passaged cell lines under in vitro selection forces and are thus notdirectly translatable to the patient. As a result, the same chemo-therapies have been used to treat osteosarcoma for decades, and thesurvivalratehasstagnatedforthepast30yearsatlessthan70%[1].Here, we take advantage of two opportunities to stimulate rapid,clinically applicable osteosarcoma research. First, in this era oftargeted cancer drugs, we have the opportunity to develop powerfuladjuvants, or even replacements, for cytotoxic chemotherapies.Early phase human trials of targeted agents in bone and soft tissuesarcomashavedocumenteddramaticresponsesinindividualpatientsdespite disappointing overall response rates [2–4], and these caseshighlight the heterogeneous biology of sarcomas. A personalizedapproach may make the best use of targeted agents whilesimultaneously addressing this heterogeneity within a rare disease.Second, dogs provide an ideal spontaneous preclinical model.Osteosarcomas in dogs and humans have remarkable similarities inhistology, patterns of metastasis, and response to treatment, butenable rapid clinical trial enrollment due to a markedly higherincidenceandashortercourseofdiseaseindogsthaninhumans[5].In this case report we use a drug screening process to personalizetherapyforanindividualdogwithspontaneousosteosarcoma.Wehaveestablishedandcharacterizedtheprimarytumorcellculture,predictedthemosteffectivetargetedagentand treatedthecaninepatientwiththeindicated tyrosine kinase inhibitor dasatinib. The process describedhere provides the foundation for an ongoing proof-of-concept clinicaltrialofpersonalizedmedicineforcanineosteosarcoma,whichishopedto ultimately translate to human clinical trials. |
| Databáze: | OpenAIRE |
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