Pronóstico de metástasis por células tumorales circulantes (CTCs).

Transcripción

1 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)

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4 Circulating Tumor Cells CTCs

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

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

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

9 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

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

11 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.

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

14 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

15 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

16 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

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

18 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% PATIENTS 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)

19 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

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23 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

24 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

25 Gracias por su atención.

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