| Title: |
DIPG-16. COMBINATION OF ARGININE DEPLETION AND POLYAMINE INHIBITION AS AN ANTICANCER STRATEGY FOR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) |
| Authors: |
Khan, Aaminah; Gamble, Laura; Pandher, Ruby; Burns, Mark R; Mussai, Francis; Norris, Murray; Haber, Michelle; Tsoli, Maria; Ziegler, David S |
| Source: |
Neuro-Oncology ; volume 22, issue Supplement_3, page iii290-iii290 ; ISSN 1522-8517 1523-5866 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2020 |
| Description: |
DIPG is an aggressive pediatric brainstem tumor, with a median survival below 12 months. Tumor cells are dependent upon arginine, a semi-essential amino acid, metabolised by arginase enzymes into ornithine, a pivotal precursor to the polyamine pathway. Polyamines, frequently upregulated in cancer, are intracellular polycations controlling key biological processes – the inhibition of which we have previously shown to be highly efficacious in preclinical DIPG models. Pegylated arginase (BCT-100) has recently been shown to significantly delay tumor development, prolonging survival of neuroblastoma-prone Th-MYCN mice. This study investigated the effects of arginine depletion therapy as a single agent and in combination with polyamine pathway inhibitors in DIPG. We found that ARG2, the gene encoding for arginase II, is expressed significantly more highly in DIPG tumors compared to normal brain. Arginine depletion via BCT-100 reduced DIPG cell proliferation and colony formation in patient-derived cell lines. Using orthotopic patient-derived xenograft models of DIPG, we found that frequent dosing of BCT-100 (4x/week) significantly delayed tumor development and increased the survival of the mice (p |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/neuonc/noaa222.066 |
| Availability: |
https://doi.org/10.1093/neuonc/noaa222.066; http://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_3/iii290/34686583/noaa222.066.pdf |
| Rights: |
http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.49CC60FE |
| Database: |
BASE |