Tackling cancer heterogeneity with systemically delivered oncolytic adenoviruses transcriptionally targeted with hybrid promoters.

ABSTRACT: Tumor escape driven by cancer heterogeneity is a hallmark of human malignancies. Oncolytic adenoviruses (OAds) are transcriptionally targeted to selectively replicate in cancer cells through the use of tumor-specific promoters (TSPs). The aim of our study was to establish whether we can tackle cancer heterogeneity with OAds transcriptionally targeted with hybrid TSPs (hTSPs). Following a comprehensive bioinformatic and molecular screening process, we identified the A33 and vWA2 promoters (Prs) as optimal candidates to combine them to construct an hTSP to drive the replication of a novel OAd named AR2015. To validate its efficacy, we evaluated AR2015 in various human colorectal cancer (CRC) cell lines, patient-derived cells, and nude mouse models and compared it with two OAds driven by sing

SUBMITTER: Russo-Maenza MA 

PROVIDER: S-EPMC12634845 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature