New research shows that CDK8 and CDK19 kinases play a key role in helping ovarian cancer cells survive after detaching from the primary tumor, a process called anoikis resistance that drives metastasis. Normally, detached cells die, but resistant ovarian cancer cells survive in the peritoneal fluid, spread to other organs, and become more aggressive.
The study found that this resistance is not caused by permanent genetic mutations but by a temporary “memory state” where cells reprogram gene expression. Resistant cells became more migratory, chemoresistant, and reliant on mitochondrial energy (oxidative phosphorylation), while also evading the immune system by hiding from T cells. Inhibitors targeting CDK8/19 were able to prevent and even reverse this resistance, re-sensitizing the cancer cells to cell death.
Because CDK8/19 inhibitors are already in clinical trials for other cancers, these findings suggest a promising new approach for advanced ovarian cancer. Targeting these transcriptional “switches” could slow metastasis, overcome chemoresistance, and improve immune recognition of tumors.