The application of deep quantitative proteomics to diagnosis, risk stratification, treatment guidance, and therapeutic resistance surveillance will revolutionize how we practice medicine. It has become clear that nucleic acid-based sequencing approaches alone are insufficient to capture the dynamic functional biochemical aberrations that characterize human disease. Importantly, essentially all current drug targets are proteins, and thus a precision pathology approach to proteomics is urgently needed.
In the first part of my talk, I will show examples of how we apply deep mass spec-based proteomics together with genomics and transcriptomics to characterize gastrointestinal (GI) tumors (such as colon cancer), to develop new prognostic and treatment-predictive biomarkers, and to discover new protein drug targets for these diseases.
Understanding the biology of the metastatic process will be key for advancing effective therapies for lethal cancers that are frequently only diagnosed after metastasizing, such as colonic adenocarcinoma. Availability of matched normal-primary-metastasis sample triples from patients is often rate-limiting in research, and thus unlocking archival FFPE (formalin-fixed paraffin-embedded) samples for deep proteome profiling will open unmatched resources for biomarker discovery. I will describe a robust deep proteome profiling method for FFPE and illustrate how we applied it to proteomic biomarker discovery in primary and matched metastatic colonic adenocarcinomas.
In the second part of my talk, I will introduce our work using proteomics to define the human autoantigen-ome, i.e., defining the totality of human proteins that can become autoantigens and elicit a humoral antibody response. We have developed an approach that uses a patient's tissue samples jointly with the same patient's serum antibodies to catalogue the patient-specific autoantigen-ome in both health and disease. We have applied this approach to patients with autoimmune disorders (such as lupus) but also to cancer patients. Our novel approach promises to become a powerful diagnostic and dynamic monitoring tool for such patients and offers tremendous potential for understanding the response to novel immuno-oncology checkpoint inhibitors.
The development of Proteome-Based Precision Diagnostics and Theranostics in Pathology will revolutionize how diseases are analyzed, classified, treated, and monitored.