LIQUID BIOPSY ANALYSIS UNIT

biopsia-liquida

The Liquid Biopsy Analysis Unit of IDIS is specialized in the analysis of different tumor elements present in biological fluids, focusing mainly on the characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Interest in the study of tumor material present in biological fluids has increased exponentially in the last decade, mainly because it is the least invasive and most dynamic strategy to characterize the tumors. Therefore, the different techniques for liquid biopsy analysis are considered today as a key tool to improve the clinical management of cancer patients and to better understand the molecular mechanisms which mediate tumor dissemination and progression.

Technological capacities


For CTCs analysis we use different isolation strategies depending on the tumor and the objective of the study. We have a CellSearch system (Menarini, Silicon Biosystems), wich allows us to isolate and quantify CTCs form blood of patients with different types of solid tumors. This system is the only FDA-approved for a clinical use in patients with metastatic breast, prostate and colon cancer. We also have the Parsortix microfluidic system (Angle) which is useful for isolating CTCs in an antigen-independent way. We also have a broad expertise using other CTCs isolation strategies such as RosetteSep (StemCell), Metacell or CellCollector (GILUPI), among others. We can also develop genetic characterization studies of the population of CTCs with pure or single cell populations using micromanipulation techniques.

For the study of ctDNA we use highly sensitive techniques such as BEAMing and ddPCR. With BEAMing technology, we have the capacity to determine mutations of great clinical relevance such as RAS (34 point-mutations of exons 2, 3 and 4 of NRAS and KRAS, labeled IVD), EGFR (10 mutations including T790 and C797S, marked RUO) and BRAF (V600E, marked RUO). In addition to this technology we have the Idylla system (Biocartis), which allows us to analyze mutations of RAS / BRAF (IVD) in ctDNA and a droplet digital PCR equipment (QX200, Biorad) that allows us to analyze different genetic alterations, such as mutations and CNVs from a broad panel of genes (including RAS, BRAF, EGFR, PI3KCA, MET, MYC, etc).

Services list


The platform provides the following services: plasma and PBMCs isolation by centrifugation and Ficoll gradients; extracellular vesicles (EVs) isolation; isolation and quantification of CTCs with CellSearch, Parsortix CellEllection, Metacell and Cellcollector systems; isolation of DNA /RNA from plasma and other body fluids; quantification of total cfDNA in plasma samples; gene expression studies by qRT-PCR, analysis of point mutations or CNVs by BEAMing or ddPCR on cfDNA. All these services can be performed on human samples and murine models.

TEAM


Investigador principal

Laura Muinelo Romay

Alicia Abalo Piñeiro
Técnico de Laboratorio
Ramón Lago Lestón
Técnico de Laboratorio
Manuel Abreu Rodríguez
Estudiante predoctoral
Oscar Rapado González
Estudiante predoctoral
Patricia Mondelo Macía
Estudiante predoctoral
Roberto Díaz Peña
Investigador postdoctoral

Proyectos de Investigación

Utilidad de la monitorización de BRAF y PD-L1 a través de biopsia líquida para guiar el tratamiento con inhibidores de BRAF en pacientes con melanoma. (Financiado con campaña mecenado) 2018-2020.

Biopsia líquida para la caracterización de c-Met en pacientes metastásicos. (Financiado con campaña mecenado) 2018-2020.

Aproximaciones al manejo de la enfermedad avanzanda en cáncer de endometrio a través de la identificación de biomarcadores en biopsia líquida. ISCIII (PI17/01919). 2019-2020.

Validación clínica del EPiGen kit: Un nuevo test para predecir la respuesta al tratamiento del Cáncer de Pulmón No Microcítico (CPNM). EPIGEN-KIT Ministerio de Economía, Industria y Competitividad. 2017- 2019.

TruePrime-LB: un método innovador para la amplificación de DNA en biopsias líquidas. Ministerio de Economía, Industria y Competitividad (RTC-2016-5092-1). 2016-2018.

Descubrimiento y desarrollo biomarcadores innovadores para medicina personalizada y terapias para el tratamiento eficaz del cáncer de pulmón. Ministerio de Ciencia e Innovación (RTC-2014-1532-1). 2014-2017.

Una nueva biopsia líquida: la saliva como herramienta clínica para el cáncer colorrectal. Financiado parcialmente por Fundación Eugenio Rodríguez Pascual. 2016-2019.

Evaluación clínica de OncoBEAM mediante el panel extendido de 34 mutaciones de RAS: Comparación de la determinación de la mutación RAS en ADN tumoral circulante y en muestra de tejido en pacientes con cáncer colorrectal metastásico. 2017-2018.

Ensayos clínicos/contratos de servicio

Estudio prospectivo de la utilidad de la biopsia líquida como factor predictor y pronóstico en pacientes con carcinoma urotelial metastásico en progresión tras quimioterapia basada en platino” SOG-PLA-2016-01 SOGUG. 2017-2018.

ERMES: ERbitux MEtastatic colorectal cancer Strategy Study; A phase III randomized two arm study with FOLFIRI + Cetuximab until disease progression compared to FOLFIRI + Cetuximab for 8 cycles followed by Cetuximab alone until disease progression in first line treatment of patients with RAS and BRAF wild type metastatic colorectal cancer. 2017-2018.

Análisis del estado de RAS en plasma de pacientes con cáncer colorrectal metastásico para la selección de tratamiento con anti-EGFR. Contrato financiado por MERCK.

Francois-Climent Bidard, Stefan Michiels, Sabine Riethdorf, Volkmar Mueller, Laura J Esserman, Anthony Lucci, Bjørn Naume, Jun Horiguchi, Rafael Gisbert-Criado, Stefan Sleijfer, Masakazu Toi, Jose A Garcia-Saenz, Andreas Hartkopf, Daniele Generali, Françoise Rothé, Jeffrey Smerage, Laura Muinelo-Romay, Justin Stebbing, Patrice Viens et al. CTCs in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst. 2018. IF: 12,6/D1

Lousada-Fernández F, Rapado-Gonzalez O, Lopez-Cedrún JL, López-López R, Muinelo-Romay L, Suarez-Cunqueiro MM. Liquid Biopsy in Oral Cancer
Int J Mol Sci. 2018 Jun 8;19(6). pii: E1704. doi: 10.3390/ijms19061704. IF 3,7/Q2

Rapado-González Ó, Majem B, Muinelo-Romay L, Álvarez-Castro A, Santamaría A, Gil-Moreno A, López-López R, Suárez-Cunqueiro MM. Human salivary microRNAs in Cancer. J Cancer. 2018 Jan 6;9(4):638-649. doi: 10.7150/jca.21180 IF: 3,2/Q2

Alonso-Alconada L, Barbazan J, Candamio S, Falco JL, Anton C, Martin-Saborido C, Fuster G, Sampedro M, Grande C, Lado R, Sampietro-Colom L, Crego E, Figueiras S, Leon-Mateos L, Lopez-Lopez R, Abal M. PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system. Clin Transl Oncol. 2017 Oct 20. doi: 10.1007/s12094-017-1760-9. IF: 2,1/Q3

Climent MÁ, Pérez-Valderrama B, Mellado B, Fernández Parra EM, Fernández Calvo O, Ochoa de Olza M, Muinelo Romay L, Anido U, Domenech M, Hernando Polo S, Arranz Arija JÁ, Caballero C, Juan Fita MJ, Castellano D. Weekly cabazitaxel plus prednisone is effective and less toxic for ‘unfit’ metastatic castration-resistant prostate cancer: Phase II Spanish Oncology Genitourinary Group (SOGUG) trial. Eur J Cancer. 2017 Dec; 87:30-37. IF: 6/Q1

Leon-Mateos L, Casas H, Abalo A, Vieito M, Abreu M, Anido U, Gomez-Tato A, Lopez-Lopez R, Abal M, Muinelo-Romay L. Improving circulating tumor cells enumeration and characterization to predict outcome in first line chemotherapy mCRPC patients. Oncotarget. 2017 May 19;8(33):54708-54721. doi: 10.18632/oncotarget.18025. IF: 5/Q1

Insua YV, Camara J, Vazquez EB, Fernandez A, Rivera FV, Silva MJVV, Barbazan J, Muinelo-Romay L, Folgar SC, Abalo A, Lopez-Lopez R, Abal M, Alonso-Alconada L. Predicting Outcome and Therapy Response in mCRC Patients Using an Indirect Method for CTCs Detection by a Multigene Expression Panel: A Multicentric Prospective Validation Study. Int J Mol Sci. 2017 Jun 13;18(6). pii: E1265. doi: 10.3390/ijms18061265. IF: 3,3/Q2

Figueras A, Alsina-Sanchís E, Lahiguera A, Abreu M, Muinelo-Romay L, Moreno-Bueno G, Casanovas O, Graupera M, Matias-Guiu X, Vidal A, Villanueva A, Viñals F. A role for CXCR4 in peritoneal and hematogenous ovarian cancer dissemination. Mol Cancer Ther. 2017; doi: 10.1158/1535-7163. IF 5,7/Q1

Salvador F, Martin A, López-Menéndez C, Moreno-Bueno G, Santos V, Vazquez-Naharro A, Santamaría PG, Morales S, Dubus P, Muinelo-Romay L, López López R, Tung JC, Weaver VM, Portillo F, Cano A. Lysyl oxidase-like protein LOXL2 promotes lung metastasis of breast cancer. Cancer Res. 2017;77(21):5846-5859; doi: 10.1158/0008-5472.CAN-16-3152; IF=8,6/D1

Vidal J*, Muinelo L*, Dalmases A, Jones F, Edelstein D, Iglesias M, Orrillo M, Abalo A, Rodríguez C, Brozos E, Vidal Y, Candamio S, Vázquez F, Ruiz J, Guix M, Visa L, Sikri V, Albanell J, Bellosillo B, Lopez-Lopez R, Montagut C. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Annals Oncol. 2017;28(6):1325-1332. doi: 10.1093/annonc/mdx125 *Co-authorship. IF=11,8/D1

Mariscal J, Alonso-Nocelo M, Muinelo-Romay L, Barbazan J, Vieito M, Abalo A, Gomez-Tato A, Maria de Los Angeles CC, Garcia-Caballero T, Rodriguez C, Brozos E, Baron F, Lopez-Lopez R, Abal M. Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer. Sci Rep. 2016 Nov 30;6:37820. doi: 10.1038/srep37820. IF=5,2/Q1

León-Mateos L, Vieito M, Anido U, López López R, Muinelo Romay L. Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back. Int J Mol Sci. 2016 Sep 20;17(9). pii: E1580. IF: 3,2/Q2

Rapado-González Ó, Majem B, Muinelo-Romay L, López-López R, Suarez-Cunqueiro MM. Cancer Salivary Biomarkers for Tumours Distant to the Oral Cavity. Int J Mol Sci. 2016; 17(9). pii: E1531. doi: 10.3390/ijms17091531. IF: 3,2/Q2

Vila A, Abal M, Muinelo-Romay L, Rodriguez-Abreu C, Rivas J, López-López R, Costa C. EGFR-Based Immunoisolation as a Recovery Target for Low-EpCAM CTC Subpopulation. PLoS One. 2016 Oct 6;11(10):e0163705. doi: 10.1371/journal.pone.0163705. IF=3,1/Q1


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