| Literature DB >> 33563661 |
Yana Pikman1,2, Sarah K Tasian3,4, Maria Luisa Sulis5,6, Kristen Stevenson7, Traci M Blonquist7, Beth Apsel Winger8, Todd M Cooper9, Melinda Pauly10, Kelly W Maloney11, Michael J Burke12, Patrick A Brown13, Nathan Gossai14, Jennifer L McNeer15, Neerav N Shukla6, Peter D Cole16,17, Justine M Kahn5, Jing Chen5,18, Matthew J Barth19, Jeffrey A Magee20, Lisa Gennarini16, Asmani A Adhav21, Catherine M Clinton21, Nicole Ocasio-Martinez21, Giacomo Gotti21, Yuting Li21, Shan Lin21, Alma Imamovic22, Cristina E Tognon23, Tasleema Patel3, Haley L Faust3, Cristina F Contreras3, Anjali Cremer21,24, Wilian A Cortopassi25, Diego Garrido Ruiz25, Matthew P Jacobson25, Neekesh V Dharia21,2,22, Angela Su26, Amanda L Robichaud21, Amy Saur Conway21, Katherine Tarlock9, Elliot Stieglitz8, Andrew E Place21,2, Alexandre Puissant26, Stephen P Hunger3,4, Annette S Kim27, Neal I Lindeman27, Lia Gore11, Katherine A Janeway21,2, Lewis B Silverman21,2, Jeffrey W Tyner23, Marian H Harris28, Mignon L Loh8, Kimberly Stegmaier1,2,22.
Abstract
Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. SIGNIFICANCE: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations.See related commentary by Bornhauser and Bourquin, p. 1322.This article is highlighted in the In This Issue feature, p. 1307. ©2021 American Association for Cancer Research.Entities:
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Year: 2021 PMID： 33563661 PMCID： PMC8178162 DOI： 10.1158/2159-8290.CD-20-0564
Source DB: PubMed Journal: Cancer Discov ISSN： 2159-8274 Impact factor: 38.272