Hypoxia-inducible factor 1A inhibition overcomes castration resistance of prostate tumors.

ABSTRACT: Androgen deprivation therapy (ADT) is a cornerstone of prostate cancer (PCa) management. Although tumors initially regress, many progress to a hormone-independent state termed castration-resistant PCa (CRPC), for which treatment options are limited. We here report that the major luminal cell population in tumors of Pten^(i)pe-/- mice, generated by luminal epithelial cell-specific deletion of the tumor suppressor PTEN after puberty, is castration-resistant and that the expression of inflammation and stemness markers is enhanced in persistent luminal cells. In addition, hypoxia-inducible factor 1 (HIF1) signaling, which we have previously demonstrated to be induced in luminal cells of Pten^(i)pe-/- mice and to promote malignant progression, is further activated. Important

SUBMITTER: Terzic J 

PROVIDER: S-EPMC10245031 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature