Synergistic antitumor activity of pan-PI3K inhibition and immune checkpoint blockade in bladder cancer.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) induces durable response in approximately 20% of patients with advanced bladder urothelial cancer (aUC). Over 50% of aUCs harbor genomic alterations along the phosphoinositide 3-kinase (PI3K) pathway. The goal of this project was to determine the synergistic effects and mechanisms of action of PI3K inhibition and ICB combination in aUC.

Methods

Alterations affecting the PI3K pathway were examined in The Cancer Genome Atlas (TCGA) and the Cancer Dependency Map databases. Human and mouse cells with Pten deletion were used for in vitro studies. C57BL/6 mice carrying syngeneic tumors were used to determine in vivo activity, mechanisms of action and secondary resistance of pan-PI3K inhibition, ICB and combination.

Results

SUBMITTER: Zhu S 

PROVIDER: S-EPMC8562536 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature