Data from Identification of <i>IGF2</i> as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma

• DOI: 10.1158/1535-7163.c.6534814.v1
• Publication Date: 2023-04-03T13:49:36Z
• Authors: Jordi Abril-Forna...; Laura Torrens; Carmen Andreu-Oller; Juan Carrillo-Rei...; Alex Rialdi; Ugne Balaseviciute; Roser Pinyol; Carla Montironi; Philipp K. Haber; Álvaro Del Río-Ál...; Montserrat Doming...; Laura Royo; Nicholas K. Akers; Catherine E. Will...; Judit Peix; Miguel Torres-Martin; Marc Puigvehi; Stefano Cairo; Margaret Childs; Rudolf Maibach; Rita Alaggio; Piotr Czauderna; Bruce Morland; Bojan Losic; Vincenzo Mazzaferro; Ernesto Guccione; Daniela Sia; Carolina Armengol; Josep M. Llovet
• Keywords: Hepatoblastoma

&lt;div&gt;Abstract&lt;p&gt;Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB assess efficacy molecular therapies preclinical models HB. Paired tumor adjacent tissues from 31 HBs a validation set 50 were analyzed using RNA-seq, SNP, methylation arrays. &lt;i&gt;IGF2&lt;/i&gt; overexpression was identified as top targetable driver, present 71% (22/31). IGF2&lt;sup&gt;high&lt;/sup&gt; tumors displayed progenitor cell features shorter recurrence-free survival. associated 91% cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss heterozygosity or miR483-5p overexpression. The antitumor effect xentuzumab (a monoclonal antibody targeting IGF1/2) alone combination conventional therapeutic agent cisplatin assessed lines, PDX-derived organoids xenograft murine model. showed strong synergistic effects lines. mice (&lt;i&gt;n&lt;/i&gt; = 55), induced significant decrease volume improved survival compared alone. These results suggest that IGF2 an driver that, HB, IGF1/2 inhibition induces superior than monotherapy. Overall, our study provides rationale for testing inhibitors patients overexpression.&lt;/p&gt;&lt;/div&gt;