Coexistent PTEN and PIK3CA alterations hyperactivate mTORC1 signaling in endometrial cancers and cause their selective sensitivity to mTORC1 inhibition

Key Points

• Endometrial cancers with PTEN and PIK3CA alterations exhibit hyperactivated mTORC1 signaling, indicating a unique treatment need.
• Tumors with both mutations resist PI3K and AKT inhibitors but show sensitivity to mTORC1 inhibition, revealing a critical therapeutic target.
• Assessment of coexistent PTEN and PIK3CA mutations demonstrates their role in cancer signaling pathways, emphasizing the importance of targeted treatments.
• This analysis highlights the potential for mTORC1 inhibition as a targeted strategy in specific endometrial cancers, with implications for future therapies.

Abstract