A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

Abstract

Colorectal cancer: Potential treatment for drug-resistant cases A recently identified small molecule shows promise for tackling resistance to a leading colorectal cancer drug. Three proteins that are over-expressed in colorectal cancer are epidermal growth factor receptor (EGFR), RAS and β-catenin. These proteins and their interconnected signaling pathways are therefore important therapeutic targets. EGFR is the target of the drug cetuximab, but many patients are resistant to this drug attributed to mutations in a gene that influences the signaling pathways of the three key proteins. Kang-Yell Choi at Yonsei University in Seoul, South Korea, and co-workers trialed a novel molecular drug on human colorectal cancer tissues and on mice. They confirmed that the new drug leads to reduced EGFR levels by degrading RAS and β-catenin and therefore suppresses the growth of colorectal cancer cells in samples with or without the resistant mutations.