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

E. Rossi, M. Fassan, M. Aieta, F. Zilio, R. Celadin, M. Borin, A. Grassi, L. Troiani, U. Basso, C. Barile, T. Sava, C. Lanza, L. Miatello, A. Jirillo, M. Rugge, S. Indraccolo, M. Cristofanilli, A. Amadori, R. Zamarchi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1286-1294
Number of pages9
JournalBritish Journal of Cancer
Volume107
Issue number8
DOIs
Publication statusPublished - Oct 9 2012

Keywords

  • Circulating endothelial cells (CEC)
  • Circulating tumour cells (CTC)
  • M30
  • Renal cancer
  • Sunitinib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to Sunitinib in metastatic renal cancer'. Together they form a unique fingerprint.

Cite this