ERX-208 Enhances Chemotherapy Responses in Ovarian Cancer Tissue Models
A screen of 147 approved drugs identified chemotherapy combinations with ERX-208. Patient-derived organoids, explants and xenografts provided additional models for testing the combination response.
Screening a Combination Partner
University of Texas researchers investigated how ERX-208 might complement chemotherapy in ovarian cancer. Earlier work had linked the compound to lysosomal acid lipase and endoplasmic-reticulum stress. In the present study, an in vitro screen tested ERX-208 in combination with 147 FDA-approved agents to identify combinations for further testing.
The screen found strong combination activity with several chemotherapy classes. The team then focused on platinum treatment and paclitaxel, both used in ovarian cancer. Across the ovarian cancer models tested, the combinations increased apoptosis and reduced proliferation, colony formation and invasion.
Connecting Drug Response with Stress and Repair
Reanalysis of ovarian cancer-cell transcriptomic data showed reduced expression of programs associated with DNA damage repair, DNA replication and checkpoint pathways after ERX-208 treatment. Combination experiments also showed greater DNA damage and stronger endoplasmic-reticulum stress and apoptotic signaling.
Patient-derived organoids, tumor explants and xenografts extended the testing beyond conventional cell cultures, including material from therapy-resistant tumors. These models supported enhanced antitumor activity of the combinations. The work brings tissue-based pharmacology into a candidate-treatment program: the organoid and explant results complement the molecular observations and the animal experiments used to examine the same combination strategy.