LY3023414 + abemaciclib + letrozole

This combination drug is an investigative regimen consisting of three small-molecule agents: LY3023414, abemaciclib, and letrozole. - **LY3023414** is an orally available, selective inhibitor of class I phosphoinositide 3-kinase (PI3K) isoforms and both mTORC1/2, and also inhibits DNA-dependent protein kinase (DNA-PK)[1][3]. Its mechanism aims to inhibit key signaling pathways responsible for cancer cell proliferation and survival. - **Abemaciclib** is a selective, orally administered cyclin-dependent kinase (CDK) 4/6 inhibitor, designed to block cell cycle progression in tumor cells. - **Letrozole** is an oral aromatase inhibitor used to decrease estrogen synthesis, thus suppressing growth in estrogen receptor (ER)-positive cancer cells. The combination targets three complementary mechanisms: PI3K/mTOR pathway inhibition (LY3023414), cell cycle control (abemaciclib), and endocrine/hormonal inhibition (letrozole). It has been applied in clinical research to treat recurrent endometrial cancer, particularly for cases showing resistance to PI3K, CDK4/6, or endocrine blockade. Development of LY3023414 was discontinued, and the specific trial of this combination in endometrial cancer was terminated early[1][3].

Other names

abemaciclibletrozole