Cancer therapy monitoring in xenografts by quantitative analysis of circulating tumor DNA

Biomarkers. 2012 Sep;17(6):498-506. doi: 10.3109/1354750X.2012.689133. Epub 2012 May 23.

Abstract

Context: Circulating tumor DNA (ctDNA) is a promising biomarker in cancer.

Materials and methods: We generated xenograft models of cancer and detected ctDNA in plasma by qRCR targeting human AluJ sequences.

Results: Our assay reached single cell sensitivity in vitro and a correlation between ctDNA amount and tumor size was observed in vivo. Treatment with a mitogen activated protein kinase kinase (MEK)-inhibitor (BAY 869766) reduced ctDNA levels. Using this assay, we also confirmed that high levels of cell-free DNA are found in cancer patients compared to healthy individuals.

Discussion and conclusion: We show that ctDNA may be useful biomarker for monitoring tumor growth and treatment response.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology
  • DNA / blood*
  • Diphenylamine / administration & dosage
  • Diphenylamine / analogs & derivatives
  • Female
  • Humans
  • Kinetics
  • Male
  • Mice
  • Mice, Nude
  • Real-Time Polymerase Chain Reaction / standards
  • Reference Standards
  • Sulfonamides / administration & dosage
  • Tumor Burden
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide
  • Sulfonamides
  • DNA
  • Diphenylamine