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 () and Kwok-Kin Wong ()
Additional contact information
Grit S. Herter-Sprie: Harvard Medical School
Houari Korideck: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue
Camilla L. Christensen: Harvard Medical School
Jan M. Herter: Center for Excellence in Vascular Biology, Brigham and Women’s Hospital, Harvard Medical School
Kevin Rhee: Harvard Medical School
Ross I. Berbeco: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue
David G. Bennett: Harvard Medical School, Beth Israel Deaconess Medical Center
Esra A. Akbay: Harvard Medical School
David Kozono: Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School
Raymond H. Mak: Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School
G. Mike Makrigiorgos: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue
Alec C. Kimmelman: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue
Kwok-Kin Wong: Harvard Medical School

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6870

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