@article{2c068665606248fabf7197259daa6421,
title = "An isogenic cell line panel for sequence-based screening of targeted anticancer drugs",
abstract = "We describe the creation of an isogenic cell line panel representing common cancer pathways, with features optimized for high-throughput screening. More than 1,800 cell lines from three normal human cell lines were generated using CRISPR technologies. Surprisingly, most of these lines did not result in complete gene inactivation despite integration of sgRNA at the desired genomic site. A subset of the lines harbored biallelic disruptions of the targeted tumor suppressor gene, yielding a final panel of 100 well-characterized lines covering 19 frequently lost cancer pathways. This panel included genetic markers optimized for sequence-based ratiometric assays for drug-based screening assays. To illustrate the potential utility of this panel, we developed a high-throughput screen that identified Wee1 inhibitor MK-1775 as a selective growth inhibitor of cells with inactivation of TP53. These cell lines and screening approach should prove useful for researchers studying a variety of cellular and biochemical phenomena.",
keywords = "Biochemical analysis, Biochemistry, Cancer",
author = "Cook, {Ashley L.} and Nicolas Wyhs and Surojit Sur and Blair Ptak and Maria Popoli and Laura Dobbyn and Tasos Papadopoulos and Chetan Bettegowda and Nickolas Papadopoulos and Bert Vogelstein and Shibin Zhou and Kinzler, {Kenneth W.}",
note = "Funding Information: The results shown in Table S1 are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga . The authors would like to thank Dr. Sujayita Roy and Dr. Alan Meeker of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Oncology Tissue Services Core for their assistance with IHC staining and optimization. Funding: This work was supported by the Virginia and D. K. Ludwig Fund for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, the Commonwealth Fund , the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Bloomberg Philanthropies , the Mark Foundation for Cancer Research, and NIH Cancer Center support grant P30 CA006973 , Gates Millennium Scholarship Program and the American Indian Graduate Center. Funding Information: The results shown in Table S1 are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. The authors would like to thank Dr. Sujayita Roy and Dr. Alan Meeker of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Oncology Tissue Services Core for their assistance with IHC staining and optimization. Funding: This work was supported by the Virginia and D. K. Ludwig Fund for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, the Commonwealth Fund, the Bloomberg-Kimmel Institute for Cancer Immunotherapy, Bloomberg Philanthropies, the Mark Foundation for Cancer Research, and NIH Cancer Center support grant P30 CA006973, Gates Millennium Scholarship Program and the American Indian Graduate Center. NW, ALC, SS, KWK, NP, SZ, BV, and CB participated in the design and planning of the project. NW, ALC, BP, MP, and LD performed research. NW, ALC, and KWK wrote the manuscript. BV, KWK, & NP are founders of Thrive Earlier Detection, an Exact Sciences Company. KWK and NP are consultants to Thrive Earlier Detection. BV, KWK, NP, and SZ hold equity in Exact Sciences. BV, KWK, NP, and SZ are founders of and own equity in ManaT Bio. KWK and NP are consultants to and own equity in Haystack Oncology, Neophore and Personal Genome Diagnostics. KWK, BV, NP, & SS hold equity in and are consultants to CAGE Pharma. BV is a consultant to and holds equity in Catalio Capital Management and may be a consultant to and hold equity in Haystack Oncology. BV owns equity in CAGE, Neophore, and Personal Genome Diagnostics. SZ has a research agreement with BioMed Valley Discoveries, Inc. CB is a consultant to Depuy-Synthes and Bionaut Labs. The companies named above, as well as other companies, have licensed previously described technologies related to the work described in this paper from Johns Hopkins University. BV, KWK, NP, CB, and SS are inventors on some of these technologies. Licenses to these technologies are or will be associated with equity or royalty payments to the inventors as well as to Johns Hopkins University. Patent applications on the work described in this paper may be filed by Johns Hopkins University. The terms of all these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. We worked to ensure diversity in experimental samples through the selection of the cell lines. One or more authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = jun,
day = "17",
doi = "10.1016/j.isci.2022.104437",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "6",
}