Introduction

Activating mutations in RAF-MEK-ERK pathway are found commonly in more than 30% human tumours and 40% of melanoma. As a result, manipulation of the pathway and the factors involved in can give hugh therapeutic effects. In this blog, we will provide new insights into therapeutic use of ATP-competitive RAF inhibitors.

We broke the whole scientific paper into 4 experimental aspects, from generic sense to much more specific aspects. Following the experimental parts, we also give a mechanism and some therapeutic uses at the end.

4 experimental aspects:

1. ATP-competitive RAF inhibitors have two opposing mechanisms of action depending on cellular context.

2. Interpreting the activity of BRAF and CRAF.

3. Inhibitor binding activate wild-type RAF isoforms by inducing dimerization, membrane localization and interaction with RAS-GTP.

4. The downstream signaling is kinase-activity independent and links to direct conformational effects of inhibitors on the RAF kinase domain.