Pronóstico de metástasis por células tumorales circulantes (CTCs).

Pronóstico de metástasis por células tumorales circulantes (CTCs). José A. Lorente Acosta Director Científico GENYO (Centro Pfizer - Universidad de Granada Junta de Andalucía de Genómica e Investigación Oncológica) www.jornadasaludinvestiga.es

Circulating Tumor Cells CTCs

Step 1 SPECIFIC COLLECTION SAMPLES : SPECIFIC TUBES Step 2 ISOLATION OF CTC Step 3 DETECTION AND CHARACTERIZATION NÚMERO (contaje) CARACTERÍSTICAS FENO/GENO/RECEPT

Step 1 SPECIFIC COLLECTION SAMPLES : SPECIFIC TUBES Step 2 ISOLATION OF CTC Step 3 DETECTION AND CHARACTERIZATION

Step 1 SPECIFIC COLLECTION SAMPLES : SPECIFIC TUBES Step 2 ISOLATION OF CTC ALLOW A FULL RANGE ACCESS TO PHENOTYPICAL, GENOTYPICAL, DEVICE AND FUNCTIONAL CHARACTERIZATION OF THESE CELLS. Pores Or NMR Multimarker: EMT EPITHELIAL MARKER

PRINCIPALES PLATAFORMAS PARA EL AISLAMIENTO Y CARACTERIZACIÓN DE CTCs CellSearch R ScreenCell R

Step 1 SPECIFIC COLLECTION SAMPLES : SPECIFIC TUBES Step 2 ISOLATION OF CTC ALLOW A FULL RANGE ACCESS TO PHENOTYPE, GENOTYPE and FUNCTIONAL CHARACTERISTICS OF THESE CELLS.

Step 1 SPECIFIC COLLECTION SAMPLES : SPECIFIC TUBES Step 2 ISOLATION OF CTC Step 3 DETECTION AND CHARACTERIZATION

NÚMERO: Cancer de próstata metastásico resistente a castración Prospectivo de 219 pacientes antes de la cht CTCs antes y un mes despues de iniciada la cht 50% supervivencia: >5 CTCs: 11.5 meses <5 CTCs: 21.7 meses Se relacionó CTC/OS de Bono et al. (2008) Clin. Cancer Res. vol. 14 (19) p. 6302-6309

NÚMERO: Valor pronóstico en cáncer de colon metastásico Prospectivo, 430 pacientes //// CTCs: Antes de cht vs. Después de cht Relación entre CTCs/PFS y OS (CTCs: factor independiente) Cohen, Steven J. et al. (2008) J. Clin. Oncol. vol. 26 (19) p. 3213-3221

CTCs plasticity The initial steps of local invasion include Activation of signaling pathways that control cytoskeletal dynamics EMT Turnover of cell matrix and cell-cell junctions Tumor cell migration into the adjacent tissue (Chambers et al., 2002) MET EPITHELIAL PHENOTYPE (Brabletz, T. et al 2001) EMT F.G Ortega MET F.G Ortega EPITELIAL MESENQUIMAL

CTCs: a BACKGROUND Serrano, Ortega, Garcia-Puche, Lorente et al (2013)

RESULTS (ca. colon metastásico / bevacizumab) Characterization of CTCs based on the VEGFR expression: CTC-VEGFR POSITIVES AT BASAL LINE 30 % of CTC were negatives for VEGFR 70% of CTC were positives for VEGFR Ck vegfr positive 70% CK VEGFR negative 30% 12 10 8 6 PATIENTS 4 2 0 Negative Response Positive Response CKVEGFRpositive 14 CKVEGFRnegative 6 RECIST CRITERIA 88% of patients with CTC VEGFR+ IMPROVE PFS with positive response ================================== 83.3% of patients with CTC VEGFR- Develop negative response and short PFS Serrano, Ortega, Garcia-Puche, Lorente et al (2013)

COLABORACIONES en MARCHA HOSPITALES: Almería, Córdoba, Granada, Jaén Málaga Barcelona. SERVICIOS: Oncología Med/RT, Urología, Cir.Digestiva, Ginecología, Anatomía Patológica, Cir. Torácica. IND. FARMACEUTICA: Amgen, Janssen, Pfizer, Roche, Pangaea, Sanofi

GROUP OF BYODINAMIC OF CIRCULATING TUMOR CELLS, MICROENVIOREMENT AND METASTASIS at GENYO Division of CIRCULATING TUMOR CELLS Group Director & Principal Investigator : Prof. JOSE A. LORENTE, M.D., Ph.D. Division Scientific Director: Dra Mª JOSE SERRANO Division Clinical Director: Prof. Dr. JOSE LUIS GARCIA-PUCHE Clinical Associates: José Manuel Cózar/ Armando Zuloaga / Juan Torres Melero/ Pedro Sánchez Rovira/ Juan de la Haba Rodríguez/ José Expósito Hernández/ Enrique Aranda/ Javier Valdivia Scientific staff: Gabriel Ortega-Sánchez (M.S.), María Jesús Álvarez-Cubero (Ph.D.), Maria Sáiz-Guinaldo (M.S.), Juan Carlos Alvarez (Ph.D.), Lucas González Herrera(M.D.) Technical staff: Carmen Feixas

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