作者: Lara E. Davis , Nicolle E. Hofmann , Guangheng Li , Elaine T. Huang , Marc M. Loriaux
DOI: 10.1002/PBC.24512
关键词: Metastasis 、 Internal medicine 、 Tyrosine-kinase inhibitor 、 Dasatinib 、 Surgery 、 Oncology 、 Clinical trial 、 Response to treatment 、 Osteosarcoma 、 Personalized therapy 、 Medicine 、 Drug 、 Pediatrics, Perinatology, and Child Health 、 Hematology
摘要: Osteosarcomaisthemostcommonmalignantbonetumor,yettheincidenceofosteosarcomaislowenoughtoposeasignificantbarrierto the timely completion of traditionally designed clinical trials.While research laboratories continue to investigate underlyingmechanisms osteosarcoma, these experiments use multiply-passaged cell lines under in vitro selection forces and are thus notdirectly translatable patient. As a result, same chemo-therapies have been used treat osteosarcoma for decades, thesurvivalratehasstagnatedforthepast30yearsatlessthan70%[1].Here, we take advantage two opportunities stimulate rapid,clinically applicable research. First, this era oftargeted cancer drugs, opportunity develop powerfuladjuvants, or even replacements, cytotoxic chemotherapies.Early phase human trials targeted agents bone soft tissuesarcomashavedocumenteddramaticresponsesinindividualpatientsdespite disappointing overall response rates [2–4], caseshighlight heterogeneous biology sarcomas. A personalizedapproach may make best whilesimultaneously addressing heterogeneity within rare disease.Second, dogs provide an ideal spontaneous preclinical model.Osteosarcomas humans remarkable similarities inhistology, patterns metastasis, treatment, butenable rapid trial enrollment due markedly higherincidenceandashortercourseofdiseaseindogsthaninhumans[5].In case report drug screening process personalizetherapyforanindividualdogwithspontaneousosteosarcoma.Wehaveestablishedandcharacterizedtheprimarytumorcellculture,predictedthemosteffectivetargetedagentand treatedthecaninepatientwiththeindicated tyrosine kinase inhibitor dasatinib. The describedhere provides foundation ongoing proof-of-concept clinicaltrialofpersonalizedmedicineforcanineosteosarcoma,whichishopedto ultimately translate trials.