@inbook{878ce4d5acae4bd480ab83300e4e19b9,
title = "Exome sequencing of drug-resistant clones for target identification",
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.",
keywords = "Anticancer toxins, Compound resistant mutations, Forward genetics, Mismatch repair deficiency, Phenotype-based screens, Target identification, Whole-exome sequencing",
author = "Ting Han and Deepak Nijhawan",
note = "Funding Information: T.H. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. D.N. is supported by a Harold C. Simmons Cancer Center Startup Award, a Disease-Oriented Clinical Scholar award, a Damon Runyon Clinical Investigator award (CI-68-13), a grant from the Welch Foundation (I-1879), and a grant from the Harrington Discovery Institute. Publisher Copyright: {\textcopyright} Springer Science+Business Media, LLC, part of Springer Nature 2019. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
doi = "10.1007/978-1-4939-8891-4_10",
language = "English (US)",
series = "Methods in Molecular Biology",
publisher = "Humana Press Inc.",
pages = "175--187",
booktitle = "Methods in Molecular Biology",
}