Protein Biomarkers Linked to Chemotherapy Resistance in Bladder Cancer Uncovered

Recent research conducted by scientists at Baylor College of Medicine has advanced our understanding of why some muscle-invasive bladder cancers (MIBC) resist standard chemotherapy treatments. Approximately 25% of patients with MIBC benefit from current chemotherapy regimens, but identifying which tumors will respond remains a challenge. To address this, the research team performed a comprehensive molecular analysis of tumor samples, integrating genomics, transcriptomics, proteomics, and phosphoproteomics techniques. This multi-omics approach enabled the generation of detailed molecular profiles for each tumor, revealing specific patterns associated with chemoresistance.

One key finding was the role of distinct protein isoforms—slightly different versions of the same protein—in determining response to therapy. Notably, isoforms of proteins like ATAD1 and members of the RAF family were more prevalent in tumors that responded well to chemotherapy. These insights emphasize the importance of studying proteins directly, as gene or RNA analysis alone might miss critical post-translational modifications.

Furthermore, the study identified active molecular pathways in resistant tumors, such as the Wnt signaling pathway linked to GSK3B and the JAK/STAT pathway involving STAT3. These pathways could serve as potential targets for new therapies aimed at overcoming resistance. The researchers also examined tumor proteins targeted by antibody-drug conjugates (ADCs) like PD-L1, TROP2, and NECTIN-4, suggesting that combining these targeted treatments with existing therapies could enhance effectiveness based on tumor subtype.

Importantly, analysis of paired pre- and post-treatment samples revealed molecular changes after chemotherapy, including shifts in tumor subtypes and increased activity of proteins involved in cell recycling and energy metabolism, which might help tumor cells survive treatment.

Senior author Dr. Seth P. Lerner highlighted the potential clinical implications, noting that these findings could lead to better patient stratification and more personalized treatments. Overall, this research paves the way for developing biomarkers to predict treatment response and new strategies to combat therapy-resistant bladder cancers.

Source: https://medicalxpress.com/news/2025-08-protein-patterns-linked-chemotherapy-resistance.html