Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to sunitinib in metastatic renal cancer

Br J Cancer. 2012 Oct 9;107(8):1286-94. doi: 10.1038/bjc.2012.388. Epub 2012 Sep 6.

Abstract

Background: Recently, we developed an apoptotic assay for expanding the monitoring capabilities of the circulating tumour cells (CTC) test during therapy. An automated platform for computing CTCs was integrated with a mAb (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 in early apoptosis; we showed that live CTCs were associated with progression, consistent with enhanced cell migration and invasion. The test was first applied here to mRCC.

Methods: Live/apoptotic CTCs changes were measured in mRCC patients receiving first-line Sunitinib and compared with circulating endothelial cell (CEC) levels.

Results: The presence of EpCAM-positive, live CTCs predicts progression in individual mRCC patient, being associated with distant metastasis under first-line Sunitinib. Synchronous detection of CTCs and CEC levels discloses for the first time an association between their dynamic changes and outcome: a rapid increase of the CEC number as early as the first cycle of therapy is associated with CTC decrease in non-progressed patients, whereas a delayed response of CECs is related to higher CTC values in the progressed group indicating treatment failure.

Conclusion: We demonstrated that a delayed response to antiangiogenic treatment indicated by persistent detection of CECs correlates with persistent live CTCs and more aggressive disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Apoptosis
  • Biomarkers, Tumor
  • Disease Progression
  • Endothelial Cells / pathology*
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Keratin-18
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / pathology*
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Treatment Failure

Substances

  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • Indoles
  • Keratin-18
  • Pyrroles
  • Sunitinib