Drug Discovery Oncology in a Mouse: Concepts, Models and Limitations

Overview

Journal Future Sci OA

Specialty Biotechnology

Date 2021 Jul 23

PMID 34295539

Citations 5

Authors

Jason E Long

Maja Jankovic

Danilo Maddalo

Affiliations

Soon will be listed here.

Abstract

The utilization of suitable mouse models is a critical step in the drug discovery oncology workflow as their generation and use are important for target identification and validation as well as toxicity and efficacy assessments. Current murine models have been instrumental in furthering insights into the mode of action of drugs before transitioning into the clinic. Recent advancements in genome editing with the development of the CRISPR/Cas9 system and the possibility of applying such technology directly have expanded the toolkit of preclinical models available. In this review, a brief presentation of the current models used in drug discovery will be provided with a particular emphasis on the novel CRISPR/Cas9 models.

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References

Driehuis E, Van Hoeck A, Moore K, Kolders S, Francies H, Gulersonmez M . Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proc Natl Acad Sci U S A. 2019; 116(52):26580-26590. PMC: 6936689. DOI: 10.1073/pnas.1911273116. View

Dow L, Fisher J, ORourke K, Muley A, Kastenhuber E, Livshits G . Inducible in vivo genome editing with CRISPR-Cas9. Nat Biotechnol. 2015; 33(4):390-394. PMC: 4390466. DOI: 10.1038/nbt.3155. View

Barcellos-Hoff M, Aggeler J, Ram T, Bissell M . Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development. 1989; 105(2):223-35. PMC: 2948482. DOI: 10.1242/dev.105.2.223. View

Sanchez-Rivera F, Papagiannakopoulos T, Romero R, Tammela T, Bauer M, Bhutkar A . Rapid modelling of cooperating genetic events in cancer through somatic genome editing. Nature. 2014; 516(7531):428-31. PMC: 4292871. DOI: 10.1038/nature13906. View

Feldser D, Kostova K, Winslow M, Taylor S, Cashman C, Whittaker C . Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature. 2010; 468(7323):572-5. PMC: 3003305. DOI: 10.1038/nature09535. View

Guo S, Deng C . Effect of Stromal Cells in Tumor Microenvironment on Metastasis Initiation. Int J Biol Sci. 2018; 14(14):2083-2093. PMC: 6299363. DOI: 10.7150/ijbs.25720. View

Shultz L, Pearson T, King M, Giassi L, Carney L, Gott B . Humanized NOD/LtSz-scid IL2 receptor common gamma chain knockout mice in diabetes research. Ann N Y Acad Sci. 2007; 1103:77-89. DOI: 10.1196/annals.1394.002. View

Derose Y, Wang G, Lin Y, Bernard P, Buys S, Ebbert M . Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011; 17(11):1514-20. PMC: 3553601. DOI: 10.1038/nm.2454. View

Fu X, Besterman J, Monosov A, Hoffman R . Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. Proc Natl Acad Sci U S A. 1991; 88(20):9345-9. PMC: 52711. DOI: 10.1073/pnas.88.20.9345. View

10.

Wang X, Fu X, Hoffman R . A new patient-like metastatic model of human lung cancer constructed orthotopically with intact tissue via thoracotomy in immunodeficient mice. Int J Cancer. 1992; 51(6):992-5. DOI: 10.1002/ijc.2910510626. View

11.

Hollingshead M, Stockwin L, Alcoser S, Newton D, Orsburn B, Bonomi C . Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies. BMC Genomics. 2014; 15:393. PMC: 4041995. DOI: 10.1186/1471-2164-15-393. View

12.

Romero R, Sayin V, Davidson S, Bauer M, Singh S, LeBoeuf S . Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med. 2017; 23(11):1362-1368. PMC: 5677540. DOI: 10.1038/nm.4407. View

13.

Roper J, Tammela T, Malli Cetinbas N, Akkad A, Roghanian A, Rickelt S . In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol. 2017; 35(6):569-576. PMC: 5462879. DOI: 10.1038/nbt.3836. View

14.

Yu J, Bhattacharya S, Yanamandra N, Kilian D, Shi H, Yadavilli S . Tumor-immune profiling of murine syngeneic tumor models as a framework to guide mechanistic studies and predict therapy response in distinct tumor microenvironments. PLoS One. 2018; 13(11):e0206223. PMC: 6214511. DOI: 10.1371/journal.pone.0206223. View

15.

Brown K, Xue A, Mittal A, Samra J, Smith R, Hugh T . Patient-derived xenograft models of colorectal cancer in pre-clinical research: a systematic review. Oncotarget. 2016; 7(40):66212-66225. PMC: 5323228. DOI: 10.18632/oncotarget.11184. View

16.

Voskoglou-Nomikos T, Pater J, Seymour L . Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res. 2003; 9(11):4227-39. View

17.

Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C . A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2012; 1(6):508-23. DOI: 10.1158/2159-8290.CD-11-0109. View

18.

Ran F, Cong L, Yan W, Scott D, Gootenberg J, Kriz A . In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015; 520(7546):186-91. PMC: 4393360. DOI: 10.1038/nature14299. View

19.

Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, Joshi N . CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature. 2014; 514(7522):380-4. PMC: 4199937. DOI: 10.1038/nature13589. View

20.

Talmadge J, Singh R, Fidler I, Raz A . Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol. 2007; 170(3):793-804. PMC: 1864878. DOI: 10.2353/ajpath.2007.060929. View