Overview

• The Journal of Clinical Investigation published the July 2025 study led by University of Michigan researchers on CDK12/13 degraders.
• Loss of CDK12/13 in tumor cells induces transcription–replication collisions that release DNA fragments to activate the STING pathway.
• STING activation drives cytotoxic T-cell infiltration and markedly improves tumor response to immune checkpoint inhibitors in mouse models.
• Clinical sample analyses across diverse cancer types link CDK12/13 inactivation with elevated STING signaling and better immunotherapy outcomes.
• Investigators are preparing phase 1 trials to test CDK12/13 degraders in combination with checkpoint blockade in cancer patients.