Rapid proteomic analysis for solid tumors revealsLSD1 as a drug target in an end‐stage cancer patient

Abstract

Recent advances in mass spectrometry (MS)‐based technologies are now set to transform translational cancer proteomics from an idea to a practice. Here, we present a robust proteomic workflow for the analysis of clinically relevant human cancer tissues that allows quantitation of thousands of tumor proteins in several hours of measuring time and a total turnaround of a few days. We applied it to a chemorefractory metastatic case of the extremely rare urachal carcinoma. Quantitative comparison of lung metastases and surrounding tissue revealed several significantly upregulated proteins, among them lysine‐specific histone demethylase 1 (LSD1/KDM1A). LSD1 is an epigenetic regulator and the target of active development efforts in oncology. Thus, clinical cancer proteomics can rapidly and efficiently identify actionable therapeutic options. While currently described for a single case study, we envision that it can be applied broadly to other patients in a similar condition.

The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response

“…For RNA-based subtyping, NanoString is a platform that could be used on a subset of transcripts without the time-intensive steps required for RNA-seq library prep and data analysis (49). Proteomics could also provide a complementary rapid assay platform that could be completed in several days (50). Moving forward, it will be important to establish protocols to obtain and subtype PDAC samples in a clinically meaningful timeframe to inform first-line therapeutic decisions.…”

The Case for Proteomics and Phospho‐Proteomics in Personalized Cancer Medicine

“…The identification and quantification of more than 10 000 different proteins from minute amount of material, including FFPE tissues, is becoming feasible . Thus, MS‐based proteomics now enables robust, reproducible, and in‐depth profiling of the proteome with fast turnaround times, for instance requiring only 4 h for blood plasma proteomics and two and a half days for tissues …”

“…Given the time constraints in this situation, we developed a fast workflow, taking only 2.5 days from obtaining the sample to interpreted result, which is much faster than corresponding oligonucleotide‐based technology turnaround times. We employed this workflow for a patient with end‐stage urachal carcinoma patient, who had already received multiple standard chemotherapies for her primary and metastatic tumor . From the tumor and surrounding tissue, we discovered a set of upregulated proteins, whose biological roles reflected tumor biology.…”

Limited Environmental Serine Confers Sensitivity to PHGDH Inhibition in Brain Metastasis

“…[41][42][43][44][45] Comparative proteomic expression profiling of TNBC cells that differ in their capacity to colonize the brain or lung using an optimized, high-sensitivity, label-free protein expression profiling workflow quantified ~7,000 proteins per sample with excellent reproducibility. [44][45][46][47] Our analysis yielded protein expression profiles of the parental, indolent, and aggressive brain metastatic cells that segregated independently by principal component analysis, indicating that each population is phenotypically distinct (Fig. 1D).…”