Volume 126, Issue 10 pp. 2437-2447
Cancer Therapy

Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors

Paola Gazzaniga

Corresponding Author

Paola Gazzaniga

Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

Fax: +39-6-4454820

Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, 00161 Roma, ItalySearch for more papers by this author
Giuseppe Naso

Giuseppe Naso

Divisione di Oncologia Medica, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

Giuseppe Naso and Angela Gradilone contributed equally to this work

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Angela Gradilone

Angela Gradilone

Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

Giuseppe Naso and Angela Gradilone contributed equally to this work

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Enrico Cortesi

Enrico Cortesi

Divisione di Oncologia Medica, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

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Orietta Gandini

Orietta Gandini

Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

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Walter Gianni

Walter Gianni

Divisione di Geriatria, I.N.R.C.A., Sede di Roma, Via Cassia 1167, Roma

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Maria Agnese Fabbri

Maria Agnese Fabbri

Divisione di Oncologia Medica, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

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Bruno Vincenzi

Bruno Vincenzi

Divisione di Oncologia Medica, Università Campus Biomedico, Via Álvaro del Portillo 200, Roma

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Franco di Silverio

Franco di Silverio

Dipartimento di Urologia, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

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Luigi Frati

Luigi Frati

Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

Divisione di Oncologia Medica, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

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Anna Maria Aglianò

Anna Maria Aglianò

Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy

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Massimo Cristofanilli

Massimo Cristofanilli

Department of Breast Medical Oncology, UT MD Anderson Cancer Center, Houston, TX

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First published: 09 October 2009
Citations: 41

Abstract

The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch™ technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.

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