Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas

Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas

https://pubmed.ncbi.nlm.nih.gov/32997991/

LabMan
$KZIA
"Leading research from Jean Zhao DANA FARBER may elevate Paxalasib above existing approved PI3K drugs. (GDC84, is a potent inhibitor of all four catalytic isoforms - Kiapp values of 2 nM, 46 nM, 3 nM, 10 nM and 70 nM for PI3Kα, PI3Kβ, PI3Ky). Sept 29 2020 ZHAO LAB "We show that PTEN-deficient GBM largely depends on p110α for proliferation and p110β for migration. Genetic ablation of either isoform delays tumor progression in mice, but only ablating both isoforms completely blocks GBM driven by the concurrent ablation of Pten and p53. BKM120 (buparlisib) treatment only modestly prolongs survival - BKM120 extends the survival of mice bearing intracranial tumors in which p110β, but not p110α, has been genetically ablated in the Pten/p53 null glioma, indicating that BKM120 fails to inhibit p110β effectively. Our study suggests that the failure of PI3K inhibitors in GBM may be due to insufficient inhibition of p110β and indicates a need to develop brain-penetrant p110α/β inhibitors".

Just posted on the US Stock twits forum, excellent research for Paxalisib!

Regards.