| Author | Andrade, Raissa Coelho | |
| Author | Boroni, Mariana | |
| Author | Amazonas, Marion Kielmanowicz | |
| Author | Vargas, Fernando Regla | |
| Access date | 2021-08-20T15:09:04Z | |
| Available date | 2021-08-20T15:09:04Z | |
| Document date | 2021 | |
| Citation | ANDRADE, Raissa Coelho et al. New drug candidates for osteosarcoma: Drug repurposing based on gene expression signature. Computers in Biology and Medicine, v. 134, 104470, p. 1-10, May 2021. . | pt_BR |
| ISSN | 0010-4825 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/48690 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Osteosarcoma | pt_BR |
| Subject in Portuguese | Dados de expressão de microarray | pt_BR |
| Subject in Portuguese | Assinatura de expressão gênica | pt_BR |
| Subject in Portuguese | Reaproveitamento de drogas | pt_BR |
| Subject in Portuguese | Afatinib | pt_BR |
| Title | New drug candidates for osteosarcoma: Drug repurposing based on gene expression signature | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.compbiomed.2021.104470 | |
| Abstract | Osteosarcoma (OS) is an aggressive bone malignancy and the third most common cancer in adolescence. Since
the late 1970s, OS therapy and prognosis had only modest improvements, making it appealing to explore new
tools that could help ameliorate the treatment. We present a meta-analysis of the gene expression signature of
primary OS, and propose small molecules that could reverse this signature. The meta-analysis was performed
using GEO microarray series. We first compared gene expression from eleven primary OS against osteoblasts to
obtain the differentially expressed genes (DEGs). We later filtered those DEGs by verifying which ones had a
concordant direction of differential expression in a validation group of 82 OS samples versus 30 bone marrow
mesenchymal stem cells (BM-MSC) samples. A final gene expression signature of 266 genes (98 up and 168 down
regulated) was obtained. The L1000CDS2 engine was used for drug repurposing. The top molecules predicted to
reverse the signature were afatinib (PubChem CID 10184653), BRD-K95196255 (PubChem CID 3242434), DG 041 (PubChem CID 11296282) and CA-074 Me (PubChem CID 23760717). Afatinib (Gilotrif™) is currently used
for metastatic non-small-cell lung cancer with EGFR mutations, and in vitro evidence shows antineoplastic po tential in OS cells. The other three molecules have reports of antineoplastic effects, but are not currently FDA approved. Further studies are necessary to establish the potential of these drugs in OS treatment. We believe
our results can be an important contribution for the investigation of new therapeutic genetic targets and for
selecting new drugs to be tested for OS. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro (UNIRIO). Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Câncer. Divisão de Pesquisa Experimental e Translacional. Laboratório de Bioinformática e Biologia Computacional. Rio de Janeiro, RJ, Brasil / Universidade de Campinas. Grupo de Pesquisa de Medicina Experimental. Campinas, SP, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro (UNIRIO). Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Osteosarcoma | pt_BR |
| Subject | Microarray expression data | pt_BR |
| Subject | Gene expression signature | pt_BR |
| Subject | Drug repurposing | pt_BR |
| Subject | Afatinib | pt_BR |
