Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the involvement of PRIM1 in osteosarcoma by differential display, Northern and Southern hybridization, as well as fluorescence in situ hybridization (FISH) on interphase nuclei. In total, 22 pediatric oncology specimens were tested. PRIM1 was found to be amplified in 41% of the samples. PRIM1 is coamplified with the core 12q13 amplicon genes CDK4, SAS, and OS9, and was physically mapped very close to them. PRIM1 is therefore a new candidate for the role of a major target gene of 12q13 amplifications in human cancers. Genes Chromosomes Cancer 26:62-69, 1999.
 ...
PMID:Amplifications of DNA primase 1 (PRIM1) in human osteosarcoma. 1044 Oct 7

Membrane protein leucine-rich repeat containing 15 (LRRC15) is known to be expressed in several solid tumors including osteosarcoma. ABBV-085, an antibody-drug conjugate against LRRC15, conjugated to monomethyl auristatin E (MMAE) was studied in osteosarcoma patient derived xenografts (PDX) by the Pediatric Preclinical Testing Consortium (PPTC). LRRC15 expression data was obtained from PPTC RNA sequencing data for the PDX models. The TARGET database was mined for LRRC15 expression in human osteosarcoma. Protein expression was confirmed via immunohistochemistry in three PDX models. Seven osteosarcoma PDX models (OS1, OS9, OS33, OS34, OS42, OS55 and OS60) with varying LRRC15 gene expression were studied. ABBV-085 was administered at 3mg/kg (OS33), 6 mg/kg (all 7 PDX) and 12mg/kg (OS60) weekly for 4 consecutive weeks via intraperitoneal injection. Control cohorts included vehicle and an isotype MMAE-linked antibody. Tumor volumes and responses were reported using PPTC statistical analysis. OS1, OS33, OS42, OS55 and OS60 had high LRRC15 expression while OS9 and OS34 had low LRRC15 expression. ABBV-085 inhibited tumor growth in 6/7 PDX models as compared to vehicle control and significantly improved event-free survival in 5/7 models as compared to isotype controls. Two models showed maintained complete responses while all others showed progressive disease. Response correlated with LRRC15 expression. ABBV-085's antitumor activity against osteosarcoma PDX suggests LRRC15 may be a rational target for pursuing clinical trials in patients with this disease.
 ...
PMID:ABBV-085, antibody-drug conjugate targeting LRRC15, is effective in osteosarcoma: A report by the Pediatric Preclinical Testing Consortium. 3329 92