Overview

• A genome-wide CRISPR screen pinpointed JNK-pathway genes, including MAP2K7, whose loss let ER+ cancer cells keep proliferating under treatment.
• In preclinical models, JNK-deficient cells kept growing despite endocrine therapy plus CDK4/6 inhibitors and formed more metastases.
• Tumor analysis from 78 treated patients linked lower JNK activity with poorer response to the combination regimen.
• The peer-reviewed paper, published August 18 in the Journal of Experimental & Clinical Cancer Research, identifies a context-dependent tumor-suppressor role for JNK in ER+ disease.
• The team is developing ways to assess tumor JNK signaling clinically and is testing alternative therapies for patients with JNK-low tumors.