New Insights into Treatment Resistance in ER+ Breast Cancer: The Role of the JNK Pathway

Researchers at the Garvan Institute of Medical Research have made a significant discovery that could influence the future of breast cancer treatment. Their study highlights how the inactivation of a critical cellular stress response, involving the JNK pathway, enables estrogen receptor-positive (ER+) breast cancer cells to evade current therapies. ER+ breast cancer, which accounts for about 70% of all breast cancer cases, often responds well to initial treatment. However, resistance to endocrine therapies frequently leads to metastatic recurrence and mortality, with over 2,000 deaths annually in Australia.

The research team conducted a comprehensive genome-wide CRISPR knockout screen to identify genes responsible for treatment resistance. They found that when key components of the JNK pathway, including the gene MAP2K7, are disabled, cancer cells continue to grow despite receiving combination treatments such as endocrine therapy and CDK4/6 inhibitors. This disruption hampers the pathway's ability to trigger cell death or growth arrest signals, allowing tumors to survive and spread.

Further analysis of tumor samples from 78 patients confirmed that low activity of the JNK pathway correlates with poorer treatment responses. These findings suggest that assessing JNK pathway activity could serve as a predictive marker for treatment efficacy, helping clinicians tailor therapies for high-risk ER+ breast cancer patients.

Interestingly, while the JNK pathway is often associated with promoting cancer in some contexts, this study reveals it can also act as a tumor suppressor in ER+ breast cancer. The loss of pathway function appears to be a key driver of treatment resistance. The team is now exploring alternative therapeutic strategies for patients with suppressed JNK activity, aiming to develop more personalized and effective interventions.

Overall, this research paves the way for improved diagnostic tools and targeted treatments, potentially reducing recurrence rates and enhancing survival outcomes for breast cancer patients. The findings were published in the Journal of Experimental & Clinical Cancer Research (source).