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Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials.

Publication ,  Journal Article
Coleman, CN; Higgins, GS; Brown, JM; Baumann, M; Kirsch, DG; Willers, H; Prasanna, PGS; Dewhirst, MW; Bernhard, EJ; Ahmed, MM
Published in: Clin Cancer Res
July 1, 2016

There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy. For in vitro research, the clonogenic assay remains the current state-of-the-art of preclinical assays, whereas newer moderate and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient-derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies; for example, regrowth delay measures bulk tumor killing, whereas local tumor control assesses effects on CSCs. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radiochemotherapy for most tumors. Radiation models are compatible with but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapeutic agent may be different from its interaction with radiation and/or radiochemotherapy. This provides an opportunity to expand the use of molecular-targeted agents. Clin Cancer Res; 22(13); 3138-47. ©2016 AACR.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

July 1, 2016

Volume

22

Issue

13

Start / End Page

3138 / 3147

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Reproducibility of Results
  • Radiation-Sensitizing Agents
  • Radiation Tolerance
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Neoplasms
  • Molecular Targeted Therapy
  • Mice
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Coleman, C. N., Higgins, G. S., Brown, J. M., Baumann, M., Kirsch, D. G., Willers, H., … Ahmed, M. M. (2016). Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials. Clin Cancer Res, 22(13), 3138–3147. https://doi.org/10.1158/1078-0432.CCR-16-0069
Coleman, C Norman, Geoff S. Higgins, J Martin Brown, Michael Baumann, David G. Kirsch, Henning Willers, Pataje G. S. Prasanna, Mark W. Dewhirst, Eric J. Bernhard, and Mansoor M. Ahmed. “Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials.Clin Cancer Res 22, no. 13 (July 1, 2016): 3138–47. https://doi.org/10.1158/1078-0432.CCR-16-0069.
Coleman CN, Higgins GS, Brown JM, Baumann M, Kirsch DG, Willers H, et al. Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials. Clin Cancer Res. 2016 Jul 1;22(13):3138–47.
Coleman, C. Norman, et al. “Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials.Clin Cancer Res, vol. 22, no. 13, July 2016, pp. 3138–47. Pubmed, doi:10.1158/1078-0432.CCR-16-0069.
Coleman CN, Higgins GS, Brown JM, Baumann M, Kirsch DG, Willers H, Prasanna PGS, Dewhirst MW, Bernhard EJ, Ahmed MM. Improving the Predictive Value of Preclinical Studies in Support of Radiotherapy Clinical Trials. Clin Cancer Res. 2016 Jul 1;22(13):3138–3147.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

July 1, 2016

Volume

22

Issue

13

Start / End Page

3138 / 3147

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Reproducibility of Results
  • Radiation-Sensitizing Agents
  • Radiation Tolerance
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Neoplasms
  • Molecular Targeted Therapy
  • Mice
  • Humans