Countering the skin toxicities of MAPK pathway inhibitors

LUT014 — A First-in-Class Topical B-RAF Inhibitor

Mechanism of Action

The Paradoxical Effect, Harnessed

All cells use proteins that transfer signals from the outside world into the cell. A certain set of proteins, called the MAPK pathway, let cells know that they need to grow and divide. Sometimes in cancer cells this signaling goes wrong. Drugs like EGFR inhibitors and RAS inhibitors block proteins near the top of the MAPK pathway (chain) to slow tumor growth. A common side effect is an acne-like skin rash called acneiform rash. LUT014 is a gel that is applied directly to the skin, where it blocks B-RAF, a protein further down the same chain. By targeting B-RAF in skin cells, LUT014 can help reduce the rash without interfering with the cancer drug's effect on the tumor.

Diagram of the MAPK signaling pathway showing where LUT014 acts

Caution: Investigational Drug. LUT014 is an investigational drug. It has not been approved by the U.S. Food and Drug Administration (FDA) for use by the general public. It is not approved as safe or effective, and is currently for use only in clinical trials or through approved expanded access programs. The safety and effectiveness of this product have not been fully established.