Researchers at Baylor College of Medicine and the Broad Institute of MIT and Harvard have made progress in understanding HER2+ breast cancer treatment responses. In a study published in Cell Reports Medicine, they used integrated proteogenomic profiling to identify two new indicators for tumor response and potential therapeutic targets for treatment-resistant cases.
Dr. Meenakshi Anurag from Baylor highlighted the significance of proteogenomics in discovering biomarkers and understanding drug resistance mechanisms. Dr. Eric Jaehnig emphasized the potential clinical impact of predicting cancer treatment responses through pre-therapy tumor sample analysis.
The CALGB 40601 clinical trial, conducted between 2008 and 2012, tested trastuzumab, lapatinib, or their combination on 305 patients with HER2+ breast cancer. Complete response rates varied across groups: 57% for combination therapy, 45% for trastuzumab alone, and 30% for lapatinib alone.
Research biopsies from these trials were initially analyzed for RNA and DNA mutations linked to treatment response. The current study expanded this analysis by including protein and phosphoprotein data from a subset of these biopsies to explore additional biomarkers.
Pathway analysis revealed that elevated EMT and WNT-beta catenin signaling were associated with non-responsive cases. Biomarker analysis identified GPRC5A and TPBG as indicators of poor anti-HER2 therapy response.
Drs. Shankha Satpathy, Michael Gillette, and Steve Carr from the Broad Institute discussed the potential of cell surface proteins like GPRC5A and TPBG as therapeutic targets. They emphasized ongoing efforts to refine technologies for identifying such proteins in clinical samples.
Dr. Matthew J Ellis reflected on the long-term vision required in translational research, noting that technologies applied today were not available when the CALGB 40601 trial began in 2001.
Contributors to this work include researchers from institutions such as Baylor College of Medicine, University of North Carolina at Chapel Hill, Broad Institute of MIT and Harvard, National Cancer Institute, and Thomas Jefferson University Hospital.
For detailed financial sources supporting this research, refer to the publication.
