Exome sequencing of drug-resistant clones for target identification

Ting Han, Deepak Nijhawan

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.
Pages175-187
Number of pages13
DOIs
StatePublished - Jan 1 2019

Publication series

NameMethods in Molecular Biology
Volume1888
ISSN (Print)1064-3745

Fingerprint

Exome
Clone Cells
Mutation
Pharmaceutical Preparations
Colorectal Neoplasms
Phenotype
Cell Line
Proteins
In Vitro Techniques

Keywords

  • 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

Cite this

Han, T., & Nijhawan, D. (2019). Exome sequencing of drug-resistant clones for target identification. In Methods in Molecular Biology (pp. 175-187). (Methods in Molecular Biology; Vol. 1888). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-8891-4_10

Exome sequencing of drug-resistant clones for target identification. / Han, Ting; Nijhawan, Deepak.

Methods in Molecular Biology. Humana Press Inc., 2019. p. 175-187 (Methods in Molecular Biology; Vol. 1888).

Research output: Chapter in Book/Report/Conference proceedingChapter

Han, T & Nijhawan, D 2019, Exome sequencing of drug-resistant clones for target identification. in Methods in Molecular Biology. Methods in Molecular Biology, vol. 1888, Humana Press Inc., pp. 175-187. https://doi.org/10.1007/978-1-4939-8891-4_10
Han T, Nijhawan D. Exome sequencing of drug-resistant clones for target identification. In Methods in Molecular Biology. Humana Press Inc. 2019. p. 175-187. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-8891-4_10
Han, Ting ; Nijhawan, Deepak. / Exome sequencing of drug-resistant clones for target identification. Methods in Molecular Biology. Humana Press Inc., 2019. pp. 175-187 (Methods in Molecular Biology).
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