Scientists find early Wee1 role that explains inhibitor side effects

A Nature study shows Wee1 helps healthy cells start DNA replication early in the cell cycle by switching off the APC/C-CDH1 protein degradation complex. Blocking Wee1 stalls fast-dividing colon and blood cells, which may explain the toxic side effects seen in clinical trials of Wee1 inhibitors. The finding could help select patients and use lower doses.

• Wee1 suppresses the APC/C-CDH1 complex to trigger S-phase entry
• About half of cancers with inactive p53 rely on Wee1 as a backup brake
• Wee1 inhibitor side effects may stem from halting healthy cell division
• Researchers plan to test the findings in patients in ongoing trials