Exome sequencing of drug-resistant clones for target identification

Ting Han, Deepak Nijhawan

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations


Many small molecule compounds with anticancer activities are discovered through phenotype-based screens. However, discovering the targets of these small molecules has been challenging. The gold standard for target identification requires the discovery of mutations in the target protein that block the effects of small molecules in vitro as well as in vivo. Here we describe the procedures for isolating drug resistant clones using the colorectal cancer cell line HCT-116 followed by whole-exome sequencing to identify recurrent mutations associated with compound resistance. Together with downstream in vitro and in vivo validation experiments, this strategy enables rapid target discovery for cytotoxic compounds.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Number of pages13
StatePublished - 2019

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745


  • Anticancer toxins
  • Compound resistant mutations
  • Forward genetics
  • Mismatch repair deficiency
  • Phenotype-based screens
  • Target identification
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics


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