title: Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to sunitinib in metastatic renal cancer.
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.
  
  
  CONCLUSIONS
  We demonstrated that a delayed response to antiangiogenic treatment indicated by persistent detection of CECs correlates with persistent live CTCs and more aggressive disease.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Fassan
authors.forename: M
authors.initials: M
authors.lastname: Aieta
authors.forename: F
authors.initials: F
authors.lastname: Zilio
authors.forename: R
authors.initials: R
authors.lastname: Celadin
authors.forename: M
authors.initials: M
authors.lastname: Borin
authors.forename: A
authors.initials: A
authors.lastname: Grassi
authors.forename: L
authors.initials: L
authors.lastname: Troiani
authors.forename: U
authors.initials: U
authors.lastname: Basso
authors.forename: C
authors.initials: C
authors.lastname: Barile
authors.forename: T
authors.initials: T
authors.lastname: Sava
authors.forename: C
authors.initials: C
authors.lastname: Lanza
authors.forename: L
authors.initials: L
authors.lastname: Miatello
authors.forename: A
authors.initials: A
authors.lastname: Jirillo
authors.forename: M
authors.initials: M
authors.lastname: Rugge
authors.forename: S
authors.initials: S
authors.lastname: Indraccolo
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: A
authors.initials: A
authors.lastname: Amadori
authors.forename: R
authors.initials: R
authors.lastname: Zamarchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053538:Keratin-18; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D017211:Treatment Failure
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D007211:Indoles; D053538:Keratin-18; D011758:Pyrroles; D000077210:Sunitinib