Preclinical In Vivo Modeling of Pediatric Sarcoma-Promises and Limitations

Overview

Journal J Clin Med

Specialty General Medicine

Date 2021 Apr 30

PMID 33918045

Citations 9

Authors

Roland Imle

Felix K F Kommoss

Ana Banito

Affiliations

Soon will be listed here.

Abstract

Pediatric sarcomas are an extremely heterogeneous group of genetically distinct diseases. Despite the increasing knowledge on their molecular makeup in recent years, true therapeutic advancements are largely lacking and prognosis often remains dim, particularly for relapsed and metastasized patients. Since this is largely due to the lack of suitable model systems as a prerequisite to develop and assess novel therapeutics, we here review the available approaches to model sarcoma in vivo. We focused on genetically engineered and patient-derived mouse models, compared strengths and weaknesses, and finally explored possibilities and limitations to utilize these models to advance both biological understanding as well as clinical diagnosis and therapy.

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References

Jones K, Barrott J, Xie M, Haldar M, Jin H, Zhu J . The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis. Oncogene. 2016; 35(38):5021-32. PMC: 5014712. DOI: 10.1038/onc.2016.38. View

Murphy B, Yin H, Maris J, Kolb E, Gorlick R, Reynolds C . Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis. Cancer Res. 2016; 76(19):5798-5809. PMC: 5050128. DOI: 10.1158/0008-5472.CAN-16-0122. View

Allen-Rhoades W, Whittle S, Rainusso N . Pediatric Solid Tumors in Children and Adolescents: An Overview. Pediatr Rev. 2018; 39(9):444-453. DOI: 10.1542/pir.2017-0268. View

Lin P, Pandey M, Jin F, Raymond A, Akiyama H, Lozano G . Targeted mutation of p53 and Rb in mesenchymal cells of the limb bud produces sarcomas in mice. Carcinogenesis. 2009; 30(10):1789-95. PMC: 4141195. DOI: 10.1093/carcin/bgp180. View

Roberts C, Leroux M, Fleming M, Orkin S . Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell. 2002; 2(5):415-25. DOI: 10.1016/s1535-6108(02)00185-x. View

Donehower L, Harvey M, Slagle B, McArthur M, Montgomery Jr C, Butel J . Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992; 356(6366):215-21. DOI: 10.1038/356215a0. View

Mito J, Riedel R, Dodd L, Lahat G, Lazar A, Dodd R . Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma. PLoS One. 2009; 4(11):e8075. PMC: 2779485. DOI: 10.1371/journal.pone.0008075. View

Chuen Choi S, Lin D, Gout P, Collins C, Xu Y, Wang Y . Lessons from patient-derived xenografts for better in vitro modeling of human cancer. Adv Drug Deliv Rev. 2014; 79-80:222-37. DOI: 10.1016/j.addr.2014.09.009. View

Haldar M, Hancock J, Coffin C, Lessnick S, Capecchi M . A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer Cell. 2007; 11(4):375-88. DOI: 10.1016/j.ccr.2007.01.016. View

10.

Russano M, Napolitano A, Ribelli G, Iuliani M, Simonetti S, Citarella F . Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J Exp Clin Cancer Res. 2020; 39(1):95. PMC: 7254767. DOI: 10.1186/s13046-020-01601-2. View

11.

Nishijo K, Chen Q, Zhang L, McCleish A, Rodriguez A, Cho M . Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Res. 2009; 69(7):2902-11. PMC: 2789740. DOI: 10.1158/0008-5472.CAN-08-3723. View

12.

Celik H, Sciandra M, Flashner B, Gelmez E, Kayraklioglu N, Allegakoen D . Clofarabine inhibits Ewing sarcoma growth through a novel molecular mechanism involving direct binding to CD99. Oncogene. 2018; 37(16):2181-2196. PMC: 9936921. DOI: 10.1038/s41388-017-0080-4. View

13.

Guidi C, Sands A, Zambrowicz B, Turner T, Demers D, Webster W . Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice. Mol Cell Biol. 2001; 21(10):3598-603. PMC: 100281. DOI: 10.1128/MCB.21.10.3598-3603.2001. View

14.

Alaggio R, Collini P, Randall R, Barnette P, Million L, Coffin C . Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic study of 10 cases and review of literature. Pediatr Dev Pathol. 2010; 13(3):209-17. DOI: 10.2350/09-07-0673-OA.1. View

15.

Yohe M, Heske C, Stewart E, Adamson P, Ahmed N, Antonescu C . Insights into pediatric rhabdomyosarcoma research: Challenges and goals. Pediatr Blood Cancer. 2019; 66(10):e27869. PMC: 6707829. DOI: 10.1002/pbc.27869. View

16.

Hinson A, Jones R, Crose L, Belyea B, Barr F, Linardic C . Human rhabdomyosarcoma cell lines for rhabdomyosarcoma research: utility and pitfalls. Front Oncol. 2013; 3:183. PMC: 3713458. DOI: 10.3389/fonc.2013.00183. View

17.

Oristian K, Crose L, Kuprasertkul N, Bentley R, Lin Y, Williams N . Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion-Positive Rhabdomyosarcoma Accelerates Tumorigenesis. Cancer Res. 2018; 78(19):5513-5520. PMC: 6459603. DOI: 10.1158/0008-5472.CAN-17-3912. View

18.

Sesillo F, Sacco A . Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas. J Vis Exp. 2019; (151). PMC: 7832123. DOI: 10.3791/59897. View

19.

Moyer A, Yu J, Sinnwell J, Dockter T, Suman V, Weinshilboum R . Spontaneous murine tumors in the development of patient-derived xenografts: a potential pitfall. Oncotarget. 2019; 10(39):3924-3930. PMC: 6570466. DOI: 10.18632/oncotarget.27001. View

20.

Kemp C . Animal Models of Chemical Carcinogenesis: Driving Breakthroughs in Cancer Research for 100 Years. Cold Spring Harb Protoc. 2015; 2015(10):865-74. PMC: 4949043. DOI: 10.1101/pdb.top069906. View