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

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
Abstract Submission for Poster Presentation
Neuroblastoma Patient-Derived Xenografts and Cell Lines from Postmortem Blood as Models to Understand and Reverse Therapy Resistance
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).
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. First Name: Shahab
    Last Name: Asgharzadeh
    Degree(s): M.D.
    Organization: Children's Hospital of Los Angeles, Los Angeles, CA, USA
  13. First Name: Araz
    Last Name: Marachelian
    Degree(s): M.D.
    Organization: Children's Hospital of Los Angeles, Los Angeles, CA, USA
  14. 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
  15. First Name: Suzanne
    Last Name: Shusterman
    Degree(s): M.D.
    Organization: Dana-Farber/Harvard Cancer Center, Boston, MA, USA
  16. First Name: Stephen
    Middle Initial: S
    Last Name: Roberts
    Degree(s): M.D.
    Organization: Oregon Health and Science University, Portland, OR USA
  17. 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
  18. 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
BALAKRISHNA KONERU
Texas Tech University Health Sciences Center