(MENAFN) Australian researchers have uncovered a critical biological process that may explain why some cases of estrogen receptor-positive (ER+) breast cancer—the most prevalent form globally—develop resistance to standard therapies.

According to a statement issued Monday by the Garvan Institute of Medical Research, the team discovered that disabling a key stress-response mechanism in cancer cells allows tumors to sidestep treatment and continue spreading.

The study, published in Italy's Journal of Experimental & Clinical Cancer Research, pinpointed the JNK pathway—a cellular defense system that typically forces damaged cells to stop dividing or undergo programmed death in response to stressors like cancer treatments.

“When we knocked out genes involved in the JNK pathway, cancer cells continued to grow despite treatment...These cells also spread to form more metastases in preclinical models,” said first author Sarah Alexandrou of the Garvan Institute and the University of New South Wales (UNSW).

Researchers found that inactivation of the JNK pathway allowed ER+ breast cancer cells to evade the effects of endocrine therapy used in combination with CDK4/6 inhibitors, a widely used first-line treatment for high-risk patients.

This resistance mechanism was confirmed through both laboratory experiments and analysis of tumor samples from breast cancer patients, where low JNK activity consistently aligned with poor treatment outcomes.

Co-author Associate Professor Liz Caldon of the Garvan Institute and UNSW emphasized that testing for JNK pathway activity may help identify breast cancer patients unlikely to respond to standard therapy, paving the way for more tailored treatment approaches.

The discovery may pave the way for diagnostic tools and targeted therapies to improve outcomes for thousands of patients facing limited options.

MENAFN18082025000045017169ID1109942130