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Noninvasive assessment of cancer response to therapy

Nature Medicine volume 14, pages 343–349 (2008)Cite this article

Abstract

Rapid assessment of cancer response to a therapeutic regimen can determine efficacy early in the course of treatment. Although biopsies of cancer can be used to rapidly assess pharmacodynamic response, certain disease sites are less accessible to repeated biopsies. Here, we simultaneously assess response in all sites of disease within days of starting therapy by use of peptide ligands selected for their ability to discern responding from nonresponding cancers. When conjugated to near-infrared imaging agents, the HVGGSSV peptide differentiates between these two types of cancer. Rapid, noninvasive assessment of the pharmacodynamic response within cancer promises to accelerate drug development and minimize the duration of treatment with ineffective regimens in cancer patients.

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Figure 1: HVGGSSV phage binding to treated tumors.
Figure 2: HVGGSSV peptide differentiates between responding and nonresponding tumors.
Figure 3: Peptide assessment of tumor response to all TKIs.
Figure 4: Peptide binding detects response to therapy in all tumor models.

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Acknowledgements

This work was supported by US National Cancer Institute grants R01-CA89674, R01-CA112385 and R01-CA125757 (D.E.H.) and the Ingram Charitable Fund and the Vanderbilt-Ingram Cancer Center. We thank E. Ruoslahti (Burnham Institute) for the gift of T7 phage–based random peptide library and A. Kraker and P. Bailey (Pfizer) for technical assistance with mouse models of cancer.

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Authors and Affiliations

  1. Department of Radiation Oncology, School of Medicine, Vanderbilt University, 1301 22nd Avenue South, B902 TVC, Nashville, 37232, Tennessee, USA

    Zhaozhong Han, Allie Fu, Hailun Wang, Roberto Diaz, Ling Geng, Halina Onishko & Dennis E Hallahan

  2. Department of Cancer Biology, School of Medicine, Vanderbilt University, 1301 22nd Avenue South, B902 TVC, Nashville, 37232, Tennessee, USA

    Hailun Wang & Dennis E Hallahan

  3. Department of Biomedical Engineering, School of Medicine, Vanderbilt University, 1301 22nd Avenue South, B902 TVC, Nashville, 37232, Tennessee, USA

    Dennis E Hallahan

  4. Vanderbilt-Ingram Cancer Center, 1301 22nd Avenue South, B902 TVC, Nashville, 37232, Tennessee, USA

    Dennis E Hallahan

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  1. Zhaozhong Han
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  2. Allie Fu
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  7. Dennis E Hallahan
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Contributions

Z.H. and A.F. discovered and prioritized peptides. A.F., R.D. and H.O. performed all mouse imaging. H.W. and L.G. performed cell assays microscopy and histology. D.E.H. is the principle investigator and oversaw all studies.

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Correspondence to Dennis E Hallahan.

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Competing interests

A patent application to the US Patent Office entitled “Imaging cancer response by use of peptide ligands” is pending.

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Supplementary Figs. 1–3 and Supplementary Methods (PDF 12300 kb)

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Han, Z., Fu, A., Wang, H. et al. Noninvasive assessment of cancer response to therapy. Nat Med 14, 343–349 (2008). https://doi.org/10.1038/nm1691

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