Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient

Mol Oncol. 2018 Aug;12(8):1296-1307. doi: 10.1002/1878-0261.12326. Epub 2018 Jun 14.

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.

Keywords: case study; clinical proteomics; epigenetics; mass spectrometry; urachal carcinoma.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • High-Throughput Nucleotide Sequencing / economics
  • Histone Demethylases / analysis
  • Histone Demethylases / genetics*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mass Spectrometry / economics
  • Molecular Targeted Therapy / economics
  • Precision Medicine / economics
  • Proteomics* / economics
  • Time Factors
  • Up-Regulation*
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Workflow

Substances

  • Histone Demethylases
  • KDM1A protein, human

Supplementary concepts

  • Urachal cancer