PI3K/AKT/mTOR Pathway Alterations Promote Malignant Progression and Xenograft Formation in Oligodendroglial Tumors.
Animals
Brain Neoplasms
/ drug therapy
Cell Line, Tumor
Class I Phosphatidylinositol 3-Kinases
/ antagonists & inhibitors
Female
Humans
Mice
Mice, SCID
Oligodendroglioma
/ drug therapy
Phosphoinositide-3 Kinase Inhibitors
/ pharmacology
Proto-Oncogene Proteins c-akt
/ antagonists & inhibitors
Signal Transduction
/ drug effects
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Xenograft Model Antitumor Assays
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 07 2019
15 07 2019
Historique:
received:
21
12
2018
revised:
14
02
2019
accepted:
08
04
2019
pubmed:
13
4
2019
medline:
23
9
2020
entrez:
13
4
2019
Statut:
ppublish
Résumé
Oligodendroglioma has a relatively favorable prognosis, however, often undergoes malignant progression. We hypothesized that preclinical models of oligodendroglioma could facilitate identification of therapeutic targets in progressive oligodendroglioma. We established multiple oligodendroglioma xenografts to determine if the PI3K/AKT/mTOR signaling pathway drives tumor progression. Two anatomically distinct tumor samples from a patient who developed progressive anaplastic oligodendroglioma (AOD) were collected for orthotopic transplantation in mice. We additionally implanted 13 tumors to investigate the relationship between PI3K/AKT/mTOR pathway alterations and oligodendroglioma xenograft formation. Pharmacologic vulnerabilities were tested in newly developed AOD models A specimen from the tumor site that subsequently manifested rapid clinical progression contained a Activation of the PI3K/AKT/mTOR pathway is an oncogenic driver and is associated with xenograft formation in oligodendrogliomas. These findings have implications for therapeutic targeting of PI3K/AKT/mTOR pathway activation in progressive oligodendrogliomas.
Identifiants
pubmed: 30975663
pii: 1078-0432.CCR-18-4144
doi: 10.1158/1078-0432.CCR-18-4144
pmc: PMC6924174
mid: NIHMS1527044
doi:
Substances chimiques
Phosphoinositide-3 Kinase Inhibitors
0
MTOR protein, human
EC 2.7.1.1
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
AKT1 protein, human
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4375-4387Subventions
Organisme : NCI NIH HHS
ID : P50 CA165962
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227821
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2019 American Association for Cancer Research.
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