A Chemocentric Approach to the Identification of Cancer Targets

PLoS One. 2012;7(4):e35582. doi: 10.1371/journal.pone.0035582. Epub 2012 Apr 25.

Abstract

A novel chemocentric approach to identifying cancer-relevant targets is introduced. Starting with a large chemical collection, the strategy uses the list of small molecule hits arising from a differential cytotoxicity screening on tumor HCT116 and normal MRC-5 cell lines to identify proteins associated with cancer emerging from a differential virtual target profiling of the most selective compounds detected in both cell lines. It is shown that this smart combination of differential in vitro and in silico screenings (DIVISS) is capable of detecting a list of proteins that are already well accepted cancer drug targets, while complementing it with additional proteins that, targeted selectively or in combination with others, could lead to synergistic benefits for cancer therapeutics. The complete list of 115 proteins identified as being hit uniquely by compounds showing selective antiproliferative effects for tumor cell lines is provided.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Computer Simulation
  • Drug Screening Assays, Antitumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • High-Throughput Screening Assays
  • Humans
  • Inhibitory Concentration 50
  • Models, Biological*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Oncogenes*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Small Molecule Libraries