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

• Published in: British journal of cancer Vol. 107; no. 8; pp. 1286 - 1294
• Main Authors: Rossi, E, Fassan, M, Aieta, M, Zilio, F, Celadin, R, Borin, M, Grassi, A, Troiani, L, Basso, U, Barile, C, Sava, T, Lanza, C, Miatello, L, Jirillo, A, Rugge, M, Indraccolo, S, Cristofanilli, M, Amadori, A, Zamarchi, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.10.2012; Nature Publishing Group
• Subjects: 692/53/2423; 692/699/67/1059/99; 692/699/67/589/1588; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors - therapeutic use; Apoptosis; Biological and medical sciences; Biomarkers, Tumor; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Chemotherapy; Clinical Study; Disease Progression; Drug Resistance; Endothelial Cells - pathology; Epidemiology; Female; Humans; Indoles - therapeutic use; Keratin-18; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Kidney Neoplasms - secondary; Kidneys; Male; Medical prognosis; Medical research; Medical sciences; Metastasis; Middle Aged; Molecular Medicine; Neoplastic Cells, Circulating - pathology; Nephrology. Urinary tract diseases; Observational studies; Oncology; Patients; Pharmacodynamics; Prospective Studies; Pyrroles - therapeutic use; Treatment Failure; Tumors; Tumors of the urinary system; Italy; sunitinib; circulating endothelial cells (CEC); renal cancer; circulating tumour cells (CTC); M30; Antineoplastic agent; Endothelial cell; Tumoral marker; Metastasis; Sunitinib; Cancerology; Dynamics; Advanced stage; Antiangiogenic agent; Protein-tyrosine kinase; Tumor cell; Kidney disease; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Malignant tumor; Kidney cancer; Multikinase inhibitor; Cancer; Apoptosis
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2012.388

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.