Method Profile
Patient-derived cervical cancer organoids connect molecular repair hypotheses with ATP-based single-agent and combination responses.
Evaluate preclinical DNA-repair combinations in a rare cervical cancer and compare selected non-neuroendocrine models.
NECC organoids with non-NECC cervical organoids for specified comparisons; complementary TC-YIK and other cancer cell lines.
Matched vehicle conditions, dose-response profiling and a separate high-concentration combination experiment, with imaging and ATP luminescence.
Organoids
Patient-derived cervical cancer organoids, including NECC and specified non-NECC comparators.
Interventions
Olaparib, the BLM inhibitor ML216 and cisplatin; the organoid combination-validation experiment used 500 μM olaparib and 500 μM BLM inhibitor.
Measurements
ATP-based viability, bright-field images and immunofluorescence for replication-stress and repair markers.
Normalize ATP measurements to matched controls and distinguish organoid response measurements from cell-line ZIP synergy scores and mouse efficacy experiments.
Compare olaparib responses across cervical organoid backgrounds and test olaparib with BLM inhibition.
NECC and non-NECC organoid models; three technical replicates per concentration/condition in the described drug assays. An independent donor count is not provided for that comparison.
Matched vehicle, single agents and combination; cervical adenosquamous organoids provide the reported olaparib comparator.
NECC organoid olaparib IC50 was 7.47 μM versus >50 μM in the adenosquamous comparator; combined olaparib/ML216 further lowered ATP viability.
Neuroendocrine cervical cancer organoids show moderate olaparib sensitivity. Combining olaparib with BLM inhibition reduced ATP-based viability more than either agent alone; cell and fibroblast studies implicated E2F1–BLM signaling in resistance.
