New Biomarkers Uncovered for Predicting HER2+ Breast Cancer Treatment Response

Recent research led by Baylor College of Medicine and Harvard's Broad Institute has made significant advances in understanding how HER2-positive breast cancers respond to therapy. By using integrated proteogenomic profiling — analyzing DNA, RNA, proteins, and phosphoproteins — scientists identified two novel indicators that could predict how effectively the cancer will respond to treatment, as well as uncover new therapeutic targets for resistant cases.

This innovative approach offers a glimpse into a future where clinicians could tailor treatments based on comprehensive molecular profiles of a patient’s tumor. Such predictive power could help determine whether a patient would achieve complete remission and long-term disease-free survival with a particular therapy, or if alternative strategies are necessary.

The study, published in Cell Reports Medicine, emphasizes that proteogenomics enhances the discovery of meaningful biomarkers and reveals mechanisms underlying drug resistance. Co-author Dr. Meenakshi Anurag highlights that incorporating proteomics data improves understanding of protein signaling pathways, potentially guiding more effective personalized treatments.

First author Dr. Eric Jaehnig explains that analyzing tumor samples before therapy can significantly influence clinical decisions, reducing ineffective treatments and improving outcomes. The research builds upon data from the CALGB 40601 trial, which involved 305 patients receiving various HER2-targeted therapies. Previously, studies focused on DNA and RNA markers to predict response, but this new study adds protein and phosphoprotein insights, identifying certain pathways like EMT and WNT-beta catenin as associated with non-response.

The researchers pinpointed two proteins, GPRC5A and TPBG, as biomarkers linked to poor treatment response through meta-analysis across multiple datasets. These cell surface proteins have potential as targets for new therapies, especially in resistant HER2+ breast cancers.

Overall, this research underscores the importance of proteogenomics in advancing precision medicine, enabling better prediction of treatment responses and identifying novel targets within resistant tumors. The long-term goal is to integrate such molecular profiling into routine clinical practice, leading to more effective and individualized cancer care.