Sorafenib and radiation: A promising combination in colorectal cancer

Andrew W. Suen, Sandra Galoforo, Brian Marples, Michele McGonagle, Laura Downing, Alvaro A. Martinez, John M. Robertson, George D. Wilson

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Purpose: To examine the combination of radiation and the multikinase inhibitor sorafenib in human colorectal cancer cell lines and xenografts. Methods and Materials: HT29 and SW48 colorectal cancer cells were studied in vitro using MTT assays to establish the optimal timing of radiation and sorafenib. This optimal timing was then investigated in clonogenic survival assays. Xenografts were established, and the effect of a 3-week schedule of daily radiation and sorafenib was studied by growth delay. Results: Sorafenib predominantly had minimal effects on cell growth or radiation response in MTT growth assays, though growth inhibition was significantly enhanced in HT29 cells when sorafenib was administered after radiation. The highest dose of sorafenib altered the α component of the cell survival curve in clonogenic assays. The combination of radiation and sorafenib was synergistic in SW48 xenografts, with a mean time to threshold tumor size of 11.4 ± 1.0 days, 37.0 ± 9.5 days, 15.5 ± 3.2 days, and 98.0 ± 11.7 days in the control, radiation, sorafenib, and combined treatment group, respectively. The effect on HT29 tumors was additive, with mean time to threshold volume of 12.6 ± 1.1 days, 61.0 ± 4.3 days, 42.6 ± 11.7 days, and 100.2 ± 12.4 days. Conclusions: Sorafenib had little effect on radiation response in vitro but was highly effective when combined with radiation in vivo, suggesting that inhibition of proliferation and interference with angiogenesis may be the basis for the interaction.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume78
Issue number1
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

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Keywords

  • Growth delay
  • Radiation
  • Sorafenib
  • Targeted agents
  • Xenograft

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Suen, A. W., Galoforo, S., Marples, B., McGonagle, M., Downing, L., Martinez, A. A., Robertson, J. M., & Wilson, G. D. (2010). Sorafenib and radiation: A promising combination in colorectal cancer. International Journal of Radiation Oncology Biology Physics, 78(1), 213-220. https://doi.org/10.1016/j.ijrobp.2010.02.064