A case study of personalized therapy for osteosarcoma

作者: Lara E. Davis , Nicolle E. Hofmann , Guangheng Li , Elaine T. Huang , Marc M. Loriaux

DOI: 10.1002/PBC.24512

关键词: MetastasisInternal medicineTyrosine-kinase inhibitorDasatinibSurgeryOncologyClinical trialResponse to treatmentOsteosarcomaPersonalized therapyMedicineDrugPediatrics, Perinatology, and Child HealthHematology

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.

参考文章(10)
S. J. Withrow, R. M. Wilkins, Cross talk from pets to people: translational osteosarcoma treatments. Ilar Journal. ,vol. 51, pp. 208- 213 ,(2010) , 10.1093/ILAR.51.3.208
Elizabeth Fox, Richard Aplenc, Rochelle Bagatell, Meredith K. Chuk, Eva Dombi, Wendy Goodspeed, Anne Goodwin, Marie Kromplewski, Nalini Jayaprakash, Marcelo Marotti, Kathryn H. Brown, Barbara Wenrich, Peter C. Adamson, Brigitte C. Widemann, Frank M. Balis, A Phase 1 Trial and Pharmacokinetic Study of Cediranib, an Orally Bioavailable Pan–Vascular Endothelial Growth Factor Receptor Inhibitor, in Children and Adolescents With Refractory Solid Tumors Journal of Clinical Oncology. ,vol. 28, pp. 5174- 5181 ,(2010) , 10.1200/JCO.2010.30.9674
Xuefeng Liu, Virginie Ory, Sandra Chapman, Hang Yuan, Chris Albanese, Bhaskar Kallakury, Olga A. Timofeeva, Caitlin Nealon, Aleksandra Dakic, Vera Simic, Bassem R. Haddad, Johng S. Rhim, Anatoly Dritschilo, Anna Riegel, Alison McBride, Richard Schlegel, ROCK Inhibitor and Feeder Cells Induce the Conditional Reprogramming of Epithelial Cells The American Journal of Pathology. ,vol. 180, pp. 599- 607 ,(2012) , 10.1016/J.AJPATH.2011.10.036
M. Serena Benassi, Lara Molendini, Gabriella Gamberi, Paola Ragazzini, M. Rosa Sollazzo, Mara Merli, Julia Asp, Giovanna Magagnoli, Alba Balladelli, Franco Bertoni, Piero Picci, Alteration of prb/p16/cdk4 regulation in human osteosarcoma International Journal of Cancer. ,vol. 84, pp. 489- 493 ,(1999) , 10.1002/(SICI)1097-0215(19991022)84:5<489::AID-IJC7>3.0.CO;2-D
Lara E. Davis, Motomi Mori, Charles Keller, Personalized cancer care: Opportunities and challenges in pediatric neuro-oncology† Pediatric Blood & Cancer. ,vol. 59, pp. 1- 2 ,(2012) , 10.1002/PBC.24018
M. Overholtzer, P. H. Rao, R. Favis, X.-Y. Lu, M. B. Elowitz, F. Barany, M. Ladanyi, R. Gorlick, A. J. Levine, The presence of p53 mutations in human osteosarcomas correlates with high levels of genomic instability Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 11547- 11552 ,(2003) , 10.1073/PNAS.1934852100
Tohru Hosoyama, Koichi Nishijo, Suresh I. Prajapati, Guangheng Li, Charles Keller, Rb1 Gene Inactivation Expands Satellite Cell and Postnatal Myoblast Pools Journal of Biological Chemistry. ,vol. 286, pp. 19556- 19564 ,(2011) , 10.1074/JBC.M111.229542
Richard Aplenc, Susan M. Blaney, Lewis C. Strauss, Frank M. Balis, Suzanne Shusterman, Ashish Mark Ingle, Shruti Agrawal, Junfeng Sun, John J. Wright, Peter C. Adamson, Pediatric Phase I Trial and Pharmacokinetic Study of Dasatinib: A Report From the Children's Oncology Group Phase I Consortium Journal of Clinical Oncology. ,vol. 29, pp. 839- 844 ,(2011) , 10.1200/JCO.2010.30.7231
Roy S. Herbst, S. Gail Eckhardt, Razelle Kurzrock, Scot Ebbinghaus, Peter J. O'Dwyer, Michael S. Gordon, William Novotny, Meredith A. Goldwasser, Tanyifor M. Tohnya, Bert L. Lum, Avi Ashkenazi, Adrian M. Jubb, David S. Mendelson, Phase I Dose-Escalation Study of Recombinant Human Apo2L/TRAIL, a Dual Proapoptotic Receptor Agonist, in Patients With Advanced Cancer Journal of Clinical Oncology. ,vol. 28, pp. 2839- 2846 ,(2010) , 10.1200/JCO.2009.25.1991
Razelle Kurzrock, Amita Patnaik, Joseph Aisner, Terri Warren, Stephen Leong, Robert Benjamin, S. Gail Eckhardt, Joseph E. Eid, Gerard Greig, Kai Habben, Cinara D. McCarthy, Lia Gore, A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clinical Cancer Research. ,vol. 16, pp. 2458- 2465 ,(2010) , 10.1158/1078-0432.CCR-09-3220