New VPC-led Study Published in Nature Communications Analyzes the Global Proteome of Muscle-Invasive Bladder Cancer In The Context of Neoadjuvant Platinum-based Chemotherapy.

[Vancouver, March 10th 2025] – A recent study has uncovered proteomic subtypes of muscle-invasive bladder cancer (MIBC), offering new insights into tumour biology, chemotherapy response, and potential therapeutic targets. Led by Dr. Peter Black’s team at the Vancouver Prostate Centre (VPC) and Dr. Gregg Morin’s group at the BC Cancer Research Centre (BCCRC), the research analyzed tumours from 107 patients using proteomics, revealing key molecular features linked to treatment outcomes.

Drs. Alberto Contreras-Sanz (VPC) and Gian Luca Negri (BCCRC) analyzed the global proteome of MIBC before and after platinum-based neoadjuvant chemotherapy (NAC), the standard treatment before radical cystectomy. They identified four pre-treatment proteomic clusters with distinct biology and chemotherapy response patterns, integrating these findings with transcriptomic subtypes and immunohistochemistry.

Analysis of post-treatment tumours revealed significant proteomic plasticity, marked by increased extracellular matrix proteins and reduced keratinization. Tumours that persisted after NAC showed enrichment of several druggable targets according to their proteomic clusters, including NECTIN-4, MTOR and PARP. Additionally, high intra-tumoural proteomic heterogeneity in pre-treatment tissue correlated with worse prognosis, underscoring the complexity of tumour evolution under chemotherapy.

“This research improves our understanding of chemotherapy response and resistance in bladder cancer,” said Dr. Alberto Contreras-Sanz from VPC. “By identifying distinct proteomic clusters, we can further explore biomarkers of response and novel therapeutic strategies.”

The study was made possible through extensive multi-institutional collaborations, including between Dr. Black’s team at VPC and Dr. Morin’s group at BCCRC, whose combined expertise in proteomic profiling and translational bladder cancer research was instrumental in this research. Their work establishes a foundation for patient stratification, targeted therapies, and a platform for further investigation. Importantly, the data generated from this work has been made openly available, providing a resource for the wider research community to conduct further exploratory analyses and advance biomarker and therapeutic development.