Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models

Grit S. Herter-Sprie, Houari Korideck, Camilla L. Christensen, Jan M. Herter, Kevin Rhee, Ross I. Berbeco, David G. Bennett, Esra A. Akbay, David Kozono, Raymond H. Mak, G. Mike Makrigiorgos, Alec C. Kimmelman, Kwok Kin Wong

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Close resemblance of murine and human trials is essential to achieve the best predictive value of animal-based translational cancer research. Kras-driven genetically engineered mouse models of non-small-cell lung cancer faithfully predict the response of human lung cancers to systemic chemotherapy. Owing to development of multifocal disease, however, these models have not been usable in studies of outcomes following focal radiotherapy (RT). We report the development of a preclinical platform to deliver state-of-The-Art image-guided RT in these models. Presence of a single tumour as usually diagnosed in patients is modelled by confined injection of adenoviral Cre recombinase. Furthermore, three-dimensional conformal planning and state-of-The-Art image-guided dose delivery are performed as in humans. We evaluate treatment efficacies of two different radiation regimens and find that Kras-driven tumours can temporarily be stabilized upon RT, whereas additional loss of either Lkb1 or p53 renders these lesions less responsive to RT.

Original languageEnglish (US)
Article number5870
JournalNature communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Herter-Sprie, G. S., Korideck, H., Christensen, C. L., Herter, J. M., Rhee, K., Berbeco, R. I., Bennett, D. G., Akbay, E. A., Kozono, D., Mak, R. H., Mike Makrigiorgos, G., Kimmelman, A. C., & Wong, K. K. (2014). Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models. Nature communications, 5, [5870]. https://doi.org/10.1038/ncomms6870