Laura Weatherdon, Kate Stuart, Megan A Cassidy, Alberto Moreno de la Gándara, Hanneke Okkenhaug, Markus Muellener, Grahame Mckenzie, Simon J Cook, Rebecca Gilley
The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new inhibitor modalities and regulators of this pathway, which may be new drug targets, continues and increasingly involves cell-based screens with small molecules or genetic screens such as RNAi, CRISPR or Protein Interference...
February 21, 2024: Biochemical Journal