Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer.

ABSTRACT: The paucity of genetically informed, immunocompetent tumor models impedes evaluation of conventional, targeted, and immune therapies. By engineering mouse fallopian tube epithelial organoids using lentiviral gene transduction and/or CRISPR/Cas9 mutagenesis, we generated multiple high-grade serous tubo-ovarian cancer (HGSC) models exhibiting mutational combinations seen in patients with HGSC. Detailed analysis of homologous recombination (HR)-proficient (Trp53^-/-;Ccne1^OE;Akt2^OE;Kras^OE ), HR-deficient (Trp53^-/-;Brca1^-/-;Myc^OE ), and unclassified (Trp53^-/-;Pten^-/-;Nf1^-/- ) organoids revealed differences in in vitro properties (proliferation, differentiation

SUBMITTER: Zhang S 

PROVIDER: S-EPMC7858239 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature