Evaluation of the pan-class I phosphoinositide 3-kinase (PI3K) inhibitor copanlisib in the Pediatric Preclinical Testing Consortium in vivo models of osteosarcoma |
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| Authors: | Douglas Harrison Jonathan Gill Michael Roth Pooja Hingorani Wendong Zhang Beverly Teicher Eric Earley Stephen Erickson Gregory Gatto Raushan Kurmasheva Peter Houghton Malcolm Smith E. Anders Kolb Richard Gorlick |
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| Affiliation: | 1. Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA;2. Cancer Therapeutics Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA;3. Global Health Technologies, RTI International, Research Triangle Park, North Carolina, USA;4. Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA;5. Division of Pediatric Hematology/Oncology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA |
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| Abstract: | Copanlisib is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, with activity against all four PI3K class I isoforms (PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ). Whole-genome and RNA sequencing data have revealed several PI3K aberrations in osteosarcoma tumor samples. The in vivo anticancer effects of copanlisib were assessed in a panel of six osteosarcoma models. Copanlisib induced prolonged event-free survival in five of six osteosarcoma models; however, all models demonstrated progressive disease suggesting minimal activity. While copanlisib did not result in tumor regression, more data are needed to fully explore the role of the PI3K pathway in the pathogenesis of osteosarcoma. |
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