Australian researchers uncover cause of treatment resistance in common breast cancer

Scientists in Sydney have identified how inactivation of a stress-response pathway enables estrogen receptor-positive breast cancer cells to resist treatment, a finding that could help doctors predict therapy outcomes and tailor treatment.

Researchers at the Garvan Institute of Medical Research in Australia have pinpointed a mechanism that explains why some estrogen receptor-positive (ER+) breast cancers fail to respond to standard therapies. ER+ is the most common breast cancer subtype globally.

The study, published in Italy’s Journal of Experimental & Clinical Cancer Research, showed that shutting down the JNK pathway allows cancer cells to evade treatment. Normally, the JNK pathway functions as a cellular alarm, halting cell division or triggering self-destruction when cells are damaged, including during cancer therapy.

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

The resistance was observed not only in lab experiments but also in patient tumour samples. In those cases, low JNK activity was linked to poor treatment responses.

Associate Professor Liz Caldon, co-author from the Garvan Institute and UNSW, said the discovery could reshape treatment strategies. She noted that testing patients for JNK pathway activity could help identify those unlikely to benefit from current first-line therapies such as endocrine treatment combined with CDK4/6 inhibitors.

The findings may pave the way for more personalised therapies, potentially improving outcomes for thousands of patients diagnosed with ER+ breast cancer each year.

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