# Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition

## TL;DR

A new study shows that inhibiting CDK8/19 can prevent ovarian cancer cells from surviving and spreading in the bloodstream.

## Contribution

CDK8/19 inhibition is shown to reverse anoikis resistance and suppress ovarian cancer metastasis.

## Key findings

- Anoikis resistance in ovarian cancer cells is non-genetic and can be reversed by CDK8/19 inhibition.
- CDK8/19 inhibition disrupts transcriptional balance needed for anoikis resistance and metastasis.
- Inhibiting CDK8/19 reduces both anoikis resistance and in vivo metastatic growth in ovarian cancer.

## Abstract

Anoikis resistance, or evasion of cell death triggered by matrix detachment, is a hallmark of cancer cell survival and metastasis. We showed that repeated exposure to suspension stress followed by recovery under attached conditions leads to development of anoikis resistance. The acquisition of anoikis resistance was associated with enhanced invasion, chemoresistance, and immune evasion in vitro and distant metastasis in vivo. This acquired anoikis resistance was not genetic, persisting for a finite duration without detachment stress, but was sensitive to CDK8/19 mediator kinase inhibition that could also reverse anoikis resistance. Transcriptomic analysis revealed that CDK8/19 kinase inhibition induces bidirectional transcriptional changes in both sensitive and resistant cells, disrupting the balanced reprogramming required for anoikis adaptation and resistance by reversing some resistance-associated pathways and enhancing others. Both anoikis resistance and in vivo metastatic growth of ovarian cancers are sensitive to CDK8/19 inhibition, thereby providing a therapeutic opportunity to both prevent and suppress ovarian cancer metastasis.

New study reveals a promising drug target (CDK8/19) that could prevent and treat ovarian<br> cancer spread by blocking cancer cells’ survival in circulation.