Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #87

Submission information

Submission Number: 87

Submission ID: 193902

Submission UUID: 58dc47f1-b37f-4413-97a7-b57f03bb5ee2

Submission URI: /nci/ccdisymposium/abstract

Submission Update: /nci/ccdisymposium/abstract?token=BwkF_GYACaKOtgoLB4SWESKIjURfsQ0wVliW9D3WNWA

Created: Fri, 09/04/2026 - 16:53

Completed: Fri, 09/04/2026 - 17:12

Changed: Fri, 09/04/2026 - 17:12

Remote IP address: 10.208.24.244

Submitted by: Anonymous

Language: English

Is draft: No

Webform: Childhood Cancer Data Initiative Annual Symposium (Abstracts Submission)

Submitted to: Childhood Cancer Data Initiative Annual Symposium (Abstract Registration)

Abstract Title:	Neuroblastoma Patient-Derived Xenografts and Cell Lines from Postmortem Blood as Models to Understand and Reverse Therapy Resistance
Abstract:	Background: Patient-derived models of neuroblastoma that recapitulate therapy resistance in patients are essential for defining resistance mechanisms. We established and characterized patient derived xenografts (PDXs) and patient derived cell lines (PDCLs) from neuroblastoma patients with progressive disease established post-mortem (PD-PM). Methods: Tumor and blood samples were cultured and/or xenografted in NOD SCIDγ mice. PDCLs and PDXs were validated by STR profiling. Mutations were identified by whole-exome sequencing and telomere maintenance mechanisms by TERT qPCR, C-circle assay, and TERT break-apart FISH. Therapeutic responses were evaluated in subcutaneous xenografts. Results: PD-PM specimens showed higher engraftment rates as xenografts (68%; 21/31 specimens, 83% for PD-PM blood specimens) and had higher take rates as PDCLs (54%, 25/46 specimens) compared to diagnosis (Dx, 17%) or progressive disease (PD, 11%, P<0.001) specimens. PD-PM PDXs had higher mutation burdens than Dx PDXs (P=0.026); 33% harbored activating ALK mutations and 33% mutations in other RAS-MAPK genes. Of 20 high TERT-expressing PD-PM PDXs, 13 had MYCN amplification and 4 MYCN-non-amplified PDXs had TERT rearrangements. One PD-PM PDX was ALT-positive. Temozolomide + irinotecan responses were shorter in 3 PD-PM than Dx and PD PDXs (P<0.001). In a PD-PM PDX, O6-BG reversed temozolomide + irinotecan resistance (P=0.002), while nanoliposomal irinotecan extended event-free survival compared to irinotecan (P=0.003). Conclusions: PD-PM PDXs activate ALK or RAS-MAPK signaling, manifest high levels of chemoresistance, and provide models to study reversing neuroblastoma drug resistance. The Children’s Oncology Group (COG) panel of PDXs is freely available from the Alex's Lemonade Stand Foundation (ALSF)/COG Childhood Cancer Repository (https://cccells.org).
Authors:	First Name: Balakrishna Last Name: Koneru Degree(s): Ph.D Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Nighat Last Name: Noureen Degree(s): Ph.D Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Ashly Last Name: Hindle Degree(s): Ph.D Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Kristyn Last Name: Mccoy Degree(s): MS Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Jonas Last Name: Nance Degree(s): BS Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Diana Last Name: Ixtlamati-Nava Degree(s): BS Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Charles Last Name: Zhu Degree(s): BS Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Tenley Last Name: Lehman Degree(s): BS Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Mohamad Middle Initial: Al Last Name: Rahawan Degree(s): M.D. Organization: Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Yael Middle Initial: P Last Name: Mosse Degree(s): M.D. Organization: Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA USA First Name: John Middle Initial: M Last Name: Maris Degree(s): M.D. Organization: Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA USA First Name: Shahab Last Name: Asgharzadeh Degree(s): M.D. Organization: Children's Hospital of Los Angeles, Los Angeles, CA, USA First Name: Araz Last Name: Marachelian Degree(s): M.D. Organization: Children's Hospital of Los Angeles, Los Angeles, CA, USA First Name: Meredith Middle Initial: S Last Name: Irwin Degree(s): M.D. Organization: Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada First Name: Suzanne Last Name: Shusterman Degree(s): M.D. Organization: Dana-Farber/Harvard Cancer Center, Boston, MA, USA First Name: Stephen Middle Initial: S Last Name: Roberts Degree(s): M.D. Organization: Oregon Health and Science University, Portland, OR USA First Name: Min Middle Initial: H Last Name: Kang Degree(s): PharmD Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA First Name: Patrick Last Name: Reynolds Degree(s): M.D. Ph.D Organization: Pediatric Cancer Research Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
Presenting Author:	BALAKRISHNA KONERU
Institution:	Texas Tech University Health Sciences Center
Email Address:	balakrishna.koneru@ttuhsc.edu