Programs & Groups

Please click on the corresponding programs below

VHIO's Cancer Genomics, Molecular Oncology, and Proteomics, led by Ana Vivancos, Paolo Nuciforo, and Francesc Canals respectively, are responsible for the development of VHIO's cutting-edge core technologies and platforms. These groups also pursue, implement and develop their own independent research lines and projects.

Core Technologies Groups

Please click on the corresponding groups below

Cancer Genomics
Imagen
Ana Vivancos
Principal Investigator
Molecular Oncology
Imagen
Paolo Nuciforo
Principal Investigator
Proteomics
Imagen
Francesc Canals
Principal Investigator

Cancer Genomics Group

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Principal Investigator
Ana Vivancos

Specialized Technicians
Ginevra Caratù
Chiara Chianese
Judit Matito
Zighereda Ogbah

Bioinformatician
Francesco M. Mancuso

Bioinformatics Technical Auxiliary
Laura Muiños

Post-Doctoral Fellows
Deborah G. Lo Giacco
Miriam Navarro
Miriam Sansó

SUMMARY

VHIO's Cancer Genomics Group serves as a Core Technology laboratory. In addition, we are dedicated to translational research as well as novel genomic test development.

We provide cutting-edge applications in cancer genomics through state-of-the-art technologies and the development of novel, fully validated tests that are used in the clinical research setting (Prescreening Program). Our lab is equipped with an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD) and two NextGen Sequencers; MiSeq and HiSeq2500, Illumina.

VHIO's Prescreening Program is nucleated around the activity of two VHIO groups - our Cancer Genomics Group and Molecular Oncology led by Paulo Nuciforo, and centers on performing molecular profiling in over 1500 patients each year as potential candidates for enrollment in our Phase I clinical trials led by VHIO's Research Unit for Molecular Therapy of Cancer (UITM) – ”la Caixa”, directed by Elena Garralda (click here).

Patients' suitability for inclusion in any given clinical trial is assessed based on their respective genomic or pathologic profile. Our Group has developed and routinely implemented several tests for our Prescreening Program. Two are based on NGS: an Amplicon-seq approach to sequence 67 genes (Illumina), as well as a 400-gene capture panel. Another two are based on nCounter (Nanostring): a gene fusion panel (with the capacity of detecting over 100 recurrent gene fusions) and a Copy Number Alteration panel (detecting 59 genes). As a reflection of our dedication to excellence and quality in the services we provide, we have achieved ISO 15189 accreditation for our Amplicon-seq testing method.

Our research activities focus on developing novel multiplexed tests that are optimized to FFPE-derived nucleic acids. Once developed, they are validated and used in clinical and translational research.

We are involved in a number of translational research projects including the identification of mechanisms of resistance to targeted therapies, with particular emphasis on liquid biopsy, specifically ctDNA as well as tumor educated platelets (TEPs).

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Figure: A.- Digital PCR arises 500 times superior sensitivity compared to Next Generation Sequencing (NGS). This improvement in technology allows detection of mutations in circulating tumor DNA from plasma samples, a revolutionary technic known as liquid biopsy. B.-The amount of cell free DNA (cfDNA) in plasma is minimum but varies greatly depending on the tumor type (CRC, colorectal cancer; NSCLC, non-small cell lung cancer; GIST, gastrointestinal stroma tumors). C.- NSCLC patient follow up of tumor evolution along treatments. Measurement of EGFR sensitizing L858R and resistance T790M mutant allele frequencies (MAFs) in plasma, both increase during second generation anti-EGFR treatment (erlotinib) and are detectable 6 months prior to standard CT-Scan progression disease (PD) diagnosis; upon initiation of anti-EGFR third generation treatment (osimertinib), MAFs substantially diminish revealing a good response to treatment. Finally, total cfDNA increases upon PD, and decreases upon effectiveness of osimertinib treatment.

STRATEGIC GOALS

  • Develop and implement improved strategies for routine patient prescreening in a setting of excellence (ISO 15189 accreditation).
  • Provide cutting-edge applications in cancer genomics through the use of novel technologies and protocol development.
  • Prioritize translational projects and partnerships that reinforce VHIO's renowned excellence in oncology, such as those we are currently pursuing with our Thoracic Tumors Group, led by Enriqueta Felip, and Gastrointestinal & Endocrine Tumors Group, directed by Josep Tabernero.

HIGHLIGHTS

  • VHIO is one of the six founding partners of the Cancer Core Europe Consortium alongside the Gustave Roussy Cancer Campus Grand Paris (Villejuif, France), Cambridge Cancer Centre (Cambridge, UK), Karolinska Institute (Stockholm, Sweden), Netherlands Cancer Institute – NKI (Amsterdam, The Netherlands), and the National Center for Tumor Diseases – DKFZ-NCT (Heidelberg, Germany), and, most recently incorporating the National Cancer Institute of Milan (INT). Our group is appointed co-leader of the Consortium's Genomics Taskforce and is responsible for the alignment of genomic testing across all 7 member institutions.
    We are currently developing a 400 gene capture panel to be used by all Cancer Core Europe Consortium partners.
  • Since VHIO incorporated in-house BEAMing liquid biopsy RAS biomarker technology early in 2015, the first academic test center to do so, significant progress has been made in validating and developing liquid biopsy and Droplet Digital PCR Bio-Rad technologies for the more effective, less invasive ‘policing’ of cancer over time, in real time.
  • VHIO is one of the few centers in Europe to run such a comprehensive prescreening program. Molecular profiling in around 1500 patients per year as candidates for enrollment in UITM's early clinical trials enables our teams to more precisely match an increasing number of individual patients with a particular study.

PI PAPER PICK (full list for 2017 below)

Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel J M, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer H G, Vivancos A. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017 Oct 1;28(10):2451-2457.

García-Foncillas J, Alba E, Aranda E, Díaz-Rubio E, López-López R, Tabernero J, Vivancos A. Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review. Ann Oncol. 2017 Dec 1;28(12):2943-2949.

Dienstmann R, Elez E, Argiles G, Matos I, Sanz-Garcia E, Ortiz C, Macarulla T, Capdevila J, Alsina M, Sauri T, Verdaguer H, Vilaro M, Ruiz-Pace F, Viaplana C, Garcia A, Landolfi S, Palmer HG, Nuciforo P, Rodon J, Vivancos A, Tabernero J. Analysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights. Mol Oncol. 2017 Sep;11(9):1263-1272.

Grasselli J, Elez E, Caratù G, Matito J, Santos C, Macarulla T, Vidal J, Garcia M, Viéitez JM, Paéz D, Falcó E, Lopez Lopez C, Aranda E, Jones F, Sikri V, Nuciforo P, Fasani R, Tabernero J, Montagut C, Azuara D, Dienstmann R, Salazar R, Vivancos A. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann Oncol. 2017 Jun 1;28(6):1294-1301.

HORIZONS 2018

  • Liquid biopsy: further develop and expand our ctDNA profiling capabilities.
  • We plan to extend ctDNA profiling to other applications and tumor types, specifically by developing a new kind of adapters for sample preparation based on UMI (Unique Molecular Identifiers) and NGS, in addition to an analysis pipeline.
  • Liquid biopsy using TEP in immunotherapy.

PUBLICATIONS

  1. Pérez-Alea M, Vivancos A, Caratú G, Matito J, Ferrer B, Hernandez-Losa J, Cortés J, Muñoz E, Garcia-Patos V, Recio JA. Genetic profile of GNAQ-mutated blue melanocytic neoplasms reveals mutations in genes linked to genomic instability and the PI3K pathway. Oncotarget. 2016 May 10;7(19):28086-95. doi: 10.18632/oncotarget.8578.
  2. Arqués O, Chicote I, Puig I, Tenbaum SP, Argilés G, Dienstmann R, Fernández N, Caratù G, Matito J, Silberschmidt D, Rodon J, Landolfi S, Prat A, Espín E, Charco R, Nuciforo P, Vivancos A, Shao W, Tabernero J, Palmer HG. Tankyrase Inhibition Blocks Wnt/β-Catenin Pathway and Reverts Resistance to PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer. Clin Cancer Res. 2016 Feb 1;22(3):644-56. doi: 10.1158/1078-0432.CCR-14-3081.
  3. Ibarrola-Villava M, Fleitas T, Llorca-Cardeñosa MJ, Mongort C, Alonso E, Navarro S, Burgues O, Vivancos A, Cejalvo JM, Perez-Fidalgo JA, Roselló S, Ribas G, Cervantes A. Determination of somatic oncogenic mutations linked to target-based therapies using MassARRAY technology. Oncotarget. 2016 Apr 19;7(16):22543-55. doi: 10.18632/oncotarget.8002.
  4. Alves-Rodrigues I, Ferreira PG, Moldón A, Vivancos AP, Hidalgo E, Guigó R, Ayté J. Spatiotemporal Control of Forkhead Binding to DNA Regulates the Meiotic Gene Expression Program. Cell Rep. 2016 Feb 2;14(4):885-95. doi: 10.1016/j.celrep.2015.12.074.
  5. Vivancos A, Caratú G, Matito J, Muñoz E, Ferrer B, Hernández-Losa J, Bodet D, Pérez-Alea M, Cortés J, Garcia-Patos V, Recio JA. Genetic evolution of nevus of Ota reveals clonal heterogeneity acquiring BAP1 and TP53 mutations. Pigment Cell Melanoma Res. 2016 Mar;29(2):247-53. doi: 10.1111/pcmr.12452.

PROJECTS

  • Plataforma de medicina de precisión basada en el desarrollo y uso asistencial de aplicaciones y tecnología de Next-Next generation sequencing NNGS.
    Roche
    PI: Ana Vivancos
    2016-2018
  • Circulating tumor DNA mutational analysis as a surrogate of mutational status of tumor samples.
    Merck KGaA
    PI: Ana Vivancos
    2015-2017
  • New technologies for new treatments: liquid biopsy meets immunotheraphy
    MERCK-GOI
    PI: Ana Vivancos
    2016-2019
  • Inhibidores de la ruta WNT/BETA-catenin como prometedora terapia para el tratamiento del cáncer de pulmón.
    Instituto de Salud Carlos III
    PI: Ana Vivancos
    2015-2018

Molecular Oncology Group

Imagen

Principal Investigator
Paolo Nuciforo

Attending Physicians
Laura Comerma
Roberta Fasani

Laboratory Supervisor
Jose Jiménez

Laboratory Assistant
Mª Ángeles Díaz

Technicians
Mª del Carmen Díaz
Francisca Gallego
Xavier Guardia
Tania López
Paola Martínez
Gertrudis Sánchez
Lidia Sánchez
Garazi Serna
César Sevillano

SUMMARY

The mission of VHIO's Molecular Oncology Group is to apply state-of-the-art tissue-based technologies to basic, translational, and clinical research with a clear focus on the development and validation of novel tumor biomarkers for precision medicine against cancer. Our group also serves as one of VHIO's Core Technology Platforms and is therefore central to research performed at our Institute.

We actively participate in all research projects involving the use of human tissue collected from patients, including biomarker analyses for patient stratification and inclusion in clinical trials, tissue banking and the development of primary xenograft models.

Activities as a Core Facility in 2017: We provided support for approximately 250 clinical trials conducted at Vall d'Hebron, representing approx. 70% of all trials open at our institution. Our involvement in clinical trials ranges from the coordination of sample collection, storage and shipment, developing and running multiple assays for real-time patient inclusion, as well as pharmacodynamic monitoring and dose finding.

In 2017, we have performed more than 4000 molecular determinations on samples for patient inclusion in clinical trials and over 24,000 tests to support basic and translation research programs. We have also been the central laboratory of choice for 10 international studies, and successfully maintained the prestigious ISO15189 quality accreditation. Additionally, we have achieved the flexible scope and expansion of the catalogue of molecular tests run under accreditation.

Group research activities in 2017: We developed a predictive model based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-posiive breast cancer treated with chemo-free dual HER2 blockade (Nuciforo et al. Ann Oncol. 2017). We have also collaborated in developing recommendations on assessing TILs in different types of solid tumors (Hendry et al. Adv Anat Pathol. 2017) and in identifying an adaptive immune response gene signature predictive of clinical outcome after PD-1 blockade (Prat et al. Cancer Res. 2017).

We have explored the importance of microbiota in colorectal cancer development. By developing an in situ hybridization mRNA assay, we evidenced Fusobacterium nucleatum persistence in liver metastases of colorectal cancer patients and antibiotic response in patient-derived tumor models (Bullman et al. Science. 2017) – see Figure.

Results of the first-in-human phase I study of oral S49076, a MET/AXL/FGFR inhibitor, in advanced solid tumors were also published together with the associated pharmacodynamics readouts generated in our laboratory (Rodon et al. Eur J Cancer. 2017).

Lastly, our group is currently working on developing a multiplex in situ technology to enable a complete set of diagnostic and research immunohistochemistry and in situ hybridization markers on a single tissue slide.

Imagen

Figure: Fusobacterium nucleatum (FN) in colorectal cancer - 1 red dot = 1 bacteria RNA molecule

STRATEGIC GOALS

  • Discovery and validation of novel biomarkers using tissue-based technologies.
  • Identification of targetable alterations as part of VHIO's Prescreening Program.
  • Application of molecular pathology strategies to support early clinical drug development programs.
  • Better define molecular target epidemiology to render treatment strategies more precise.
  • Act as a central and local laboratory in clinical trials.
  • Serve as a Core Facility for VHIO research programs.

HIGHLIGHTS

  • Development of biomarker strategies for patients treated with passive (anti-HER2 antibodies) or active (anti-PD1/PD-L1) immunotherapy, FGFR, and MET clinical development programs.
  • Identification of Fusobacterium and associated microbiota in liver metastases from colorectal cancer patients and sensitivity to antibiotic therapy.
  • Maintenance and expansion of tests under ISO15189 accreditation.
  • Supported over 250 clinical trials for sample management and analyses.
  • Selected as the central laboratory for different international studies.
  • Over 4000 molecular determinations on samples for patient inclusion in clinical trials and over 24,000 tests performed for basic and translation research programs.

PI PAPER PICK (full list for 2017 below)

Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017 Dec 15;358(6369):1443-1448. doi: 10.1126/science.aal5240. Epub 2017 Nov 23.

Nuciforo P, Pascual T, Cortés J, Llombart-Cussac A, Fasani R, Paré L, Oliveira M, Galvan P, Martínez N, Bermejo B, Vidal M, Pernas S, López R, Muñoz M, Garau I, Manso L, Alarcón J, Martínez E, Rodrik-Outmezguine V, Brase JC, Villagrasa P, Prat A, Holgado E. A predictive model of pathological response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Ann Oncol. 2017 Oct 12. doi: 10.1093/annonc/mdx647. [Epub ahead of print].

Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, Fernandez-Ruiz S, Sutherland JD, Clasquin M, Tomas-Cortazar J, Jimenez J, Torres I, Quang P, Ximenez-Embun P, Bago R, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Torrano V, Cabrera D, van Liempd SM, Cendon Y, Castro E, Murray S, Revandkar A, Alimonti A, Zhang Y, Barnett A, Lein G, Pirman D, Cortazar A, Arreal L, Prudkin L, Astobiza I, Valcarcel-Jimenez L, Zuñiga-García P, Fernandez-Dominguez I, Piva M, Caro-Maldonado A, Sánchez-Mosquera P, Castillo-Martín M, Serra V, Beraza N, Gentilella A, Thomas G, Azkargorta M, Elortza F, Farràs R, Olmos D, Efeyan A, Anguita J, Muñoz J, Falcón-Pérez JM, Barrio R, Macarulla T, Mato JM, Martinez-Chantar ML, Cordon-Cardo C, Aransay AM, Marks K, Baselga J, Tabernero J, Nuciforo P, Manning BD, Marjon K, Carracedo A. MTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature. 2017 Jul 6;547(7661):109-113.

Llombart-Cussac A, Cortes J, Paré L, Galvan P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol. 2017 Apr;18(4):545-554. doi: 10.1016/S1470-2045(17)30021-9. Epub 2017 Feb 24.

HORIZONS 2018

  • Develop and validate new technologies for biomarker analyses in FFPE tissues, with special focus on target quantification and multiplex IHC.
  • Explore the impact of tumor microenvironment and microbiota in improving personalized treatment decisions.
  • Maintain and expand the number of ISO15189-accredited diagnostic tests to be used for patient selection and targeted therapies.
  • Improve processes related to clinical trial sample coordination and our internal prescreening program.

PUBLICATIONS

  1. Nuciforo P. The search for simplicity: is this compatible with precision medicine? Ann Oncol 2016. First published online: October 25, 2016 doi: 10.1093/annonc/mdw566.
  2. Llombart-Cussac A, Cortés J, Paré L, Galván P, Bermejo B, Martínez N, Vidal M, Pernas S, López R, Muñoz M, Nuciforo P, Morales S, Oliveira M, de la Peña L, Peláez A, Prat A. HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol. 2017 Apr;18(4):545-554. doi: 10.1016/S1470-2045(17)30021-9. Epub 2017 Feb 24.
  3. Cejalvo JM, Martínez de Dueñas E, Galván P, García-Recio S, Burgués Gasión O, Paré L, Antolín S, Martinello R, Blancas I, Adamo B, Guerrero-Zotano Á, Muñoz M, Nucíforo P, Vidal M, Pérez RM, Chacón López-Muniz JI, Caballero R, Peg V, Carrasco E, Rojo F, Perou CM, Cortés J, Adamo V, Albanell J, Gomis RR, Lluch A, Prat A. Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer. Cancer Res. 2017 May 1;77(9):2213-2221. doi: 10.1158/0008-5472.CAN-16-2717. Epub 2017 Mar 1.
  4. Grasselli J, Elez E, Caratù G, Matito J, Santos C, Macarulla T, Vidal J, Garcia M, Viéitez JM, Paéz D, Falcó E, Lopez Lopez C, Aranda E, Jones F, Sikri V, Nuciforo P, Fasani R, Tabernero J, Montagut C, Azuara D, Dienstmann R, Salazar R, Vivancos A. Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann Oncol. 2017 Jun 1;28(6):1294-1301. doi: 10.1093/annonc/mdx112.
  5. Prat A, Navarro A, Paré L, Reguart N, Galvan P, Pascual T, Martínez A, Nuciforo P, Comerma L, Alos L, Pardo N, Cedrés S, Fan C, Parker JS, Gaba L, Victoria I, Viñolas N, Vivancos A, Arance A, Felip E. Immune-related gene expression profiling after PD-1 blockade in non-small cell lung carcinoma, head and neck squamous cell carcinoma and melanoma. Cancer Res. 2017 May 9. pii: canres.3556.2017. doi: 10.1158/0008-5472.CAN-16-3556. [Epub ahead of print].
  6. Dienstmann R, Elez E, Argiles G, Matos I, Sanz-Garcia E, Ortiz C, Macarulla T, Capdevila J, Alsina M, Sauri T, Verdaguer H, Vilaro M, Ruiz-Pace F, Viaplana C, Garcia A, Landolfi S, Palmer HG, Nuciforo P, Rodon J, Vivancos A, Tabernero JAnalysis of mutant allele fractions in driver genes in colorectal cancer - biological and clinical insights. Mol Oncol. 2017 Sep;11(9):1263-1272. doi: 10.1002/1878-0261.12099. Epub 2017 Jul 20.
  7. Rodon J, Postel-Vinay S, Hollebecque A, Nuciforo P, Azaro A, Cattan V, Marfai L, Sudey I, Brendel K, Delmas A, Malasse S, Soria JC. First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours. Eur J Cancer. 2017 Aug;81:142-150. doi: 10.1016/j.ejca.2017.05.007.
  8. Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, Fernandez-Ruiz S, Sutherland JD, Clasquin M, Tomas-Cortazar J, Jimenez J, Torres I, Quang P, Ximenez-Embun P, Bago R, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Torrano V, Cabrera D, van Liempd SM, Cendon Y, Castro E, Murray S, Revandkar A, Alimonti A, Zhang Y, Barnett A, Lein G, Pirman D, Cortazar AR, Arreal L, Prudkin L, Astobiza I, Valcarcel-Jimenez L, Zuñiga-García P, Fernandez-Dominguez I, Piva M, Caro-Maldonado A, Sánchez-Mosquera P, Castillo-Martín M, Serra V, Beraza N, Gentilella A, Thomas G, Azkargorta M, Elortza F, Farràs R, Olmos D, Efeyan A, Anguita J, Muñoz J, Falcón-Pérez JM, Barrio R, Macarulla T, Mato JM, Martinez-Chantar ML, Cordon-Cardo C, Aransay AM, Marks K, Baselga J, Tabernero J, Nuciforo P, Manning BD, Marjon K, Carracedo A. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature. 2017 Jul 6;547(7661):109-113. doi: 10.1038/nature22964. Epub 2017 Jun 28.
  9. Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O'Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research. Adv Anat Pathol. 2017 Sep;24(5):235-251. doi: 10.1097/PAP.0000000000000162.
  10. Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O'Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors. Adv Anat Pathol. 2017 Nov;24(6):311-335. doi: 10.1097/PAP.0000000000000161.
  11. Martinez-Marti A, Felip E, Matito J, Mereu E, Navarro A, Cedrés S, Pardo N, Martinez de Castro A, Remon J, Miquel JM, Guillaumet-Adkins A, Nadal E, Rodriguez-Esteban G, Arqués O, Fasani R, Nuciforo P, Heyn H, Villanueva A, Palmer HG, Vivancos A. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 2017 Oct 1;28(10):2451-2457. doi: 10.1093/annonc/mdx396.
  12. Nuciforo P, Pascual T, Cortés J, Llombart-Cussac A, Fasani R, Paré L, Oliveira M, Galvan P, Martínez N, Bermejo B, Vidal M, Pernas S, López R, Muñoz M, Garau I, Manso L, Alarcón J, Martínez E, Rodrik-Outmezguine V, Brase JC, Villagrasa P, Prat A, Holgado E. A predictive model of pathological response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Ann Oncol. 2017 Oct 12. doi: 10.1093/annonc/mdx647. [Epub ahead of print]
  13. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017 Dec 15;358(6369):1443-1448. doi: 10.1126/science.aal5240. Epub 2017 Nov 23.

PROJECTS

  • Fusobacterium and associated microbiota in colorectal cancer.
  • Tumor-infiltrating lymphocytes as predictive markers of response to passive immunotherapy.
  • Predictive biomarkers of response to anti-HER2 therapy in gastroesophageal cancer.
  • Exploratory prognostic/predictive values of protein targets quantification in CRC using Mass Spectrometry.
  • Refining mesothelin as therapeutic target in advanced colorectal cancer.

Proteomics Group

Imagen

Principal Investigator
Francesc Canals

Post-Doctoral Fellow
Núria Colomé

Technicians
Luna Martin
Anna Sabé

Graduate Student
Marc Fernández

SUMMARY

Proteomics involves the characterization of the entire set of proteins - proteome - expressed by a particular cell or tissue under specific physiological or pathological conditions. The application of proteomic technologies to cancer research is a rapidly expanding field - not only for basic research but also for the discovery of diagnostic or disease-progression biomarkers. We mainly focus on applying proteomic techniques to the identification and characterization of substrates of metalloproteases involved in tumor progression.

Metalloproteases of the ADAM and ADAMTS families play a crucial role in the regulation of the tumor microenvironment by mediating the remodeling of the extracellular matrix and the cleavage of specific extracellular and membrane proteins. Insights into the substrates of these proteases in the context of tumor cells are required in order to elucidate their role in tumor growth and metastasis as well as evaluate their potential as therapeutic targets.

Our group employs mass spectrometry-based proteomic strategies to search for new substrates of these proteases and analyze their involvement in tumor progression.

We also adopt proteomic techniques for the screening and validation of biomarkers for cancer diagnostics, precision therapy against cancer, and the tracking of disease. Our focus centers on the development of mass spectrometry-based assays for the analysis of biomarkers in clinical samples. VHIO's Proteomics Group is a member of the Spanish Consortium Chromosome 16 HPP which forms part of the HUPO Human Proteome Project. Following a chromosome-centric strategy, this multicenter and international project aims at developing an entire map of the proteins encoded by the human genome to advance our understanding of human biology in health and disease.

As a Core Facility, we provide state-of-the-art proteomic methodologies to VHIO researchers as well as implement new developments within the field to offer the very latest proteomic strategies and technologies.

Imagen

Figure: Proteomic characterization of colorectal patient-derived xenograph (PDX) models. Proteomic and phosphoproteomic analysis of patient-derived mouse model tumors allows the molecular characterization of tumor subtypes. Colorectal tumors of MSS and MSI subtypes can be correctly classified on the basis of tumor derived proteins, phosphorylated proteins involved in signaling, or microenvironment proteins, of mouse origin in the PDX model.

STRATEGIC GOALS

  • Provide services in proteomic techniques to other research groups as a Core Facility.
  • Proteomic screening for new biomarkers to help develop cancer therapeutics.
  • Development of mass spectrometry-based assays for the analysis of biomarkers in clinical samples.
  • Contribute to mapping the Chromosome 16 proteome as part of the Human Proteome Project.

HIGHLIGHTS

  • The provision of proteomic services to VHIO groups, oncology professionals at the Vall d'Hebron University Hospital (HUVH), and members of the ProteoRed-Instituto Salud Carlos III network.
  • Setting up workflows for the proteomic and phosphoproteomic screening of CRC PDX models.
  • Participation in the Spanish Consortium Chromosome 16 HPP, the HUPO Human Proteome Project.

PI PAPER PICK (full list for 2017 below)

García-Berrocoso T, Llombart V, Colàs-Campàs L, Hainard A, Licker V, Penalba A, Ramiro L, Simats A, Bustamante A, Martínez-Saez E, Canals F, Sanchez JC, Montaner J. Single Cell Immuno-laser Microdissection Coupled to Label-free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia. Mol Cell Proteomics. 2017 Nov 13. [Epub ahead of print]

Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, Maicas M, Du S, Iorio F, Herranz-Ors C, Islam A, Prado X, Llorente A, Petit A, Vidal A, Català I, Soler T, Venturas G, Rojo-Sebastian A, Serra H, Cuadras D, Blanco I, Lozano J, Canals F, Sieuwerts AM, de Weerd V, Look MP, Puertas S, García N, Perkins AS, Bonifaci N, Skowron M, Gómez-Baldó L, Hernández V, Martínez-Aranda A, Martínez-Iniesta M, Serrat X, Cerón J, Brunet J, Barretina MP, Gil M, Falo C, Fernández A, Morilla I, Pernas S, Plà MJ, Andreu X, Seguí MA, Ballester R, Castellà E, Nellist M, Morales S, Valls J, Velasco A, Matias-Guiu X, Figueras A, Sánchez-Mut JV, Sánchez-Céspedes M, Cordero A, Gómez-Miragaya J, Palomero L, Gómez A, Gajewski TF, Cohen EE, Jesiotr M, Bodnar L, Quintela-Fandino M, López-Bigas N, Valdés-Mas R, Puente XS, Viñals F, Casanovas O, Graupera M, Hernández-Losa J, Ramón Y Cajal S, García-Alonso L, Saez-Rodriguez J, Esteller M, Sierra A, Martín-Martín N, Matheu A, Carracedo A, González-Suárez E, Nanjundan M, Cortés J, Lázaro C, Odero MD, Martens JW, Moreno-Bueno G, Barcellos-Hoff MH, Villanueva A, Gomis RR, Pujana MA. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition. Oncogene. 2017. May 11;36(19):2737-2749

Vialas V, Colomé-Calls N, Abian J, Aloria K, Alvarez-Llamas G, Antúnez O, Arizmendi JM, Azkargorta M, Barceló-Batllori S, Barderas MG, Blanco F, Casal JI, Casas V, de la Torre C, Chicano-Gálvez E, Elortza F, Espadas G, Estanyol JM, Fernandez-Irigoyen J, Fernandez-Puente P, Fidalgo MJ, Fuentes M, Gay M, Gil C, Hainard A, Hernaez ML, Ibarrola N, Kopylov AT, Lario A, Lopez JA, López-Lucendo M, Marcilla M, Marina-Ramírez A, Marko-Varga G, Martín L, Mora MI, Morato-López E, Muñoz J, Odena MA, de Oliveira E, Orera I, Ortea I, Pasquarello C, Ray KB, Rezeli M, Ruppen I, Sabidó E, Del Pino MM, Sancho J, Santamaría E, Vazquez J, Vilaseca M, Vivanco F, Walters JJ, Zgoda VG, Corrales FJ, Canals F, Paradela A. A multicentric study to evaluate the use of relative retention times in targeted proteomics. J Proteomics. 2017 Jan 30;152:138-149.

Llombart V, Trejo SA, Bronsoms S, Morancho A, Feifei M, Faura J, García-Berrocoso T, Simats A, Rosell A, Canals F, Hernández-Guillamón M, Montaner J. Profiling and identification of new proteins involved in brain ischemia using MALDI-imaging-mass-spectrometry. J Proteomics. 2017Jan 30;152:243-253.

HORIZONS 2018

  • Proteomic screening for novel biomarkers towards developing cancer therapeutics. Current projects are related to ADAM and ADAMTS metalloproteases in breast cancer, and the proteomic and phosphoproteomic screening of CRC PDX models.
  • Development of MS-based assays to monitor cancer biomarkers in clinical samples, particularly plasma and FFPE samples.
  • Continued involvement in the HUPO Human Proteome Project through the Spanish Chromosome 16 HPP Consortium.
  • Provide state-of-the art proteomic methodologies to other research groups.

PUBLICATIONS

  1. García-Berrocoso T, Llombart V, Colàs-Campàs L, Hainard A, Licker V, Penalba A, Ramiro L, Simats A, Bustamante A, Martínez-Saez E, Canals F, Sanchez JC, Montaner J. Single Cell Immuno-laser Microdissection Coupled to Label-free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia. Mol Cell Proteomics. 2017 Nov 13. [Epub ahead of print]
  2. Fraga H, Pujols J, Gil-Garcia M, Roque A, Bernardo-Seisdedos G, Santambrogio C, Bech-Serra JJ, Canals F, Bernadó P, Grandori R, Millet O, Ventura S. Disulfide driven folding for a conditionally disordered protein. Sci Rep. 2017 Dec 5;7(1):16994
  3. Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, Boni J, Maicas M, Du S, Iorio F, Herranz-Ors C, Islam A, Prado X, Llorente A, Petit A, Vidal A, Català I, Soler T, Venturas G, Rojo-Sebastian A, Serra H, Cuadras D, Blanco I, Lozano J, Canals F, Sieuwerts AM, de Weerd V, Look MP, Puertas S, García N, Perkins AS, Bonifaci N, Skowron M, Gómez-Baldó L, Hernández V, Martínez-Aranda A, Martínez-Iniesta M, Serrat X, Cerón J, Brunet J, Barretina MP, Gil M, Falo C, Fernández A, Morilla I, Pernas S, Plà MJ, Andreu X, Seguí MA, Ballester R, Castellà E, Nellist M, Morales S, Valls J, Velasco A, Matias-Guiu X, Figueras A, Sánchez-Mut JV, Sánchez-Céspedes M, Cordero A, Gómez-Miragaya J, Palomero L, Gómez A, Gajewski TF, Cohen EE, Jesiotr M, Bodnar L, Quintela-Fandino M, López-Bigas N, Valdés-Mas R, Puente XS, Viñals F, Casanovas O, Graupera M, Hernández-Losa J, Ramón Y Cajal S, García-Alonso L, Saez-Rodriguez J, Esteller M, Sierra A, Martín-Martín N, Matheu A, Carracedo A, González-Suárez E, Nanjundan M, Cortés J, Lázaro C, Odero MD, Martens JW, Moreno-Bueno G, Barcellos-Hoff MH, Villanueva A, Gomis RR, Pujana MA. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition. Oncogene 2017. May 11;36(19):2737-2749
  4. Vialas V, Colomé-Calls N, Abian J, Aloria K, Alvarez-Llamas G, Antúnez O, Arizmendi JM, Azkargorta M, Barceló-Batllori S, Barderas MG, Blanco F, Casal JI, Casas V, de la Torre C, Chicano-Gálvez E, Elortza F, Espadas G, Estanyol JM, Fernandez-Irigoyen J, Fernandez-Puente P, Fidalgo MJ, Fuentes M, Gay M, Gil C, Hainard A, Hernaez ML, Ibarrola N, Kopylov AT, Lario A, Lopez JA, López-Lucendo M, Marcilla M, Marina-Ramírez A, Marko-Varga G, Martín L, Mora MI, Morato-López E, Muñoz J, Odena MA, de Oliveira E, Orera I, Ortea I, Pasquarello C, Ray KB, Rezeli M, Ruppen I, Sabidó E, Del Pino MM, Sancho J, Santamaría E, Vazquez J, Vilaseca M, Vivanco F, Walters JJ, Zgoda VG, Corrales FJ, Canals F, Paradela A. A multicentric study to evaluate the use of relative retention times in targeted proteomics. J Proteomics. 2017 Jan 30;152:138-149.
  5. Llombart V, Trejo SA, Bronsoms S, Morancho A, Feifei M, Faura J, García-Berrocoso T, Simats A, Rosell A, Canals F, Hernández-Guillamón M, Montaner J. Profiling and identification of new proteins involved in brain ischemia using MALDI-imaging-mass-spectrometry. J Proteomics. 2017Jan 30;152:243-253.

PROJECTS

  • Plataforma de Recursos Biomoleculares y Bioinformáticos (PRB2)
    Funding Agency: Instituto de Salud Carlos III (ISCIII)
    Reference: PT13/0001
    Duration: 01/01/2014 - 31/12/2017