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PLEIO-RANK SIGNED

Pleiotropic treatment of cancer: RANK inhibitors targeting cancer stem cells and immunity

Total Cost €

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EC-Contrib. €

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Partnership

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 PLEIO-RANK project word cloud

Explore the words cloud of the PLEIO-RANK project. It provides you a very rough idea of what is the project "PLEIO-RANK" about.

models    solid    tissue    cells    regulate    tolerance    patients    active    promotes    tumor    acting    expands    tumors    osteoclasts    rankl    activation    clinical    patient    therapeutic    progesterone    pleio    epithelia    outcome    crosstalk    inhibitors    dissect    breast    generation    mortality    inducible    paracrine    opposing    reduce    skin    compartment    hierarchy    tackles    bone    therapy    pool    worldwide    stemness    immunity    showed    environment    undertaking    overexpression    unexplored    synergistic    cell    immune    rank    inhibition    chronic    recurrence    validate    multiple    tumorigenesis    signaling    implications    lineage    epithelial    antitumor    hypotesize    stem    once    induce    thousands    human    contribution    homeostasis    colon    pleiotropic    cancer    xenografts    samples    interferes    how    differentiation    divergent    receptor    induces    transformed    mammary    inflammation    metastasis    induction    tracing    inhibiting    mediator    immnunosuppressive   

Project "PLEIO-RANK" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE 

Organization address
address: AVENIDA GRAN VIA HOSPITALET 199-203
city: L'HOSPITALET DE LLOBREGAT
postcode: 8908
website: www.idibell.cat

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Spain [ES]
 Total cost 1˙999˙960 €
 EC max contribution 1˙999˙960 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2021-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE ES (L'HOSPITALET DE LLOBREGAT) coordinator 1˙999˙960.00

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 Project objective

'Thousands of cancer patients worldwide are taking RANKL inhibitors for the management of bone metastasis, based on the key role of RANKL and its receptor, RANK, in osteoclasts. RANK signaling has multiple divergent effects in immunity and inflammation, both in the generation of active immune responses, as well as in the induction of tolerance. We showed that RANK overexpression induces stemness and interferes with differentiation in non transformed mammary epithelial cells and promotes mammary tumorigenesis, acting as a paracrine mediator of progesterone.

However, the therapeutic potential of inhibiting RANK signaling once tumors develop and its effects on tumor immunity remain unexplored. Our proposal tackles novel concepts: Is RANK a better therapeutic target than RANKL? Does RANK induce 'stemness' in other epithelia and solid tumors and how? Does RANK regulate the tumor-immune cell crosstalk? Would inhibition of RANK signaling in tumor and immune cells result in synergistic or opposing effects on tumor outcome? We hypotesize that RANK activation in solid tumors expands the cancer stem cells pool and induces an immnunosuppressive environment leading to tumor recurrence and metastasis.

In PLEIO-RANK we aim to: 1. Define the contribution of RANK to the epithelial hierarchy in mammary, skin and colon, during homeostasis and tumorigenesis, undertaking lineage tracing approaches. 2. Dissect the impact of RANK loss in the epithelial or the immune compartment in tumor outcome, exploiting tissue inducible models, in breast cancer and solid tumors driven by chronic inflammation. 3. Validate the clinical implications of our findings using patient derived xenografts and human tumor samples.

Based on the results of our proposal RANK inhibition could become a unique targeted therapy able to reduce metastasis and mortality in solid tumors for its pleiotropic antitumor effects in cancer stem cells, immune cells and their crosstalk.

'

 Publications

year authors and title journal last update
List of publications.
2016 Lacey E. Dobrolecki, Susie D. Airhart, Denis G. Alferez, Samuel Aparicio, Fariba Behbod, Mohamed Bentires-Alj, Cathrin Brisken, Carol J. Bult, Shirong Cai, Robert B. Clarke, Heidi Dowst, Matthew J. Ellis, Eva Gonzalez-Suarez, Richard D. Iggo, Peter Kabos, Shunqiang Li, Geoffrey J. Lindeman, Elisabetta Marangoni, Aaron McCoy, Funda Meric-Bernstam, Helen Piwnica-Worms, Marie-France Poupon, Jorge Reis-Filho, Carol A. Sartorius, Valentina Scabia, George Sflomos, Yizheng Tu, François Vaillant, Jane E. Visvader, Alana Welm, Max S. Wicha, Michael T. Lewis
Patient-derived xenograft (PDX) models in basic and translational breast cancer research
published pages: 547-573, ISSN: 0167-7659, DOI: 10.1007/s10555-016-9653-x
Cancer and Metastasis Reviews 35/4 2019-06-07
2017 Montserrat Pérez-Salvia, Laia Simó-Riudalbas, Pere Llinàs-Arias, Laura Roa, Fernando Setien, Marta Soler, Manuel Castro de Moura, James E. Bradner, Eva Gonzalez-Suarez, Catia Moutinho, Manel Esteller
Bromodomain inhibition shows antitumoral activity in mice and human luminal breast cancer
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.18255
Oncotarget 8/31 2019-06-07
2019 Roger von Moos, Luis Costa, Eva Gonzalez-Suarez, Evangelos Terpos, Daniela Niepel, Jean–Jacques Body
Management of bone health in solid tumours: From bisphosphonates to a monoclonal antibody
published pages: , ISSN: 0305-7372, DOI: 10.1016/j.ctrv.2019.05.003
Cancer Treatment Reviews 2019-06-07
2018 Zuzana Koledova, Beatrice A. Howard, Johanna Englund, Karsten Bach, Mohammed Bentires-Alj, Eva Gonzalez-Suarez
European Network of Breast Development and Cancer turned 10 years: a growing family of mammary gland researchers
published pages: , ISSN: 1465-542X, DOI: 10.1186/s13058-018-1032-9
Breast Cancer Research 20/1 2019-06-07
2016 Eva M. Trinidad, Eva González-Suárez
RANKL inhibitors for osteosarcoma treatment: hope and caution
published pages: 534-534, ISSN: 2305-5839, DOI: 10.21037/atm.2016.12.10
Annals of Translational Medicine 4/24 2019-06-07
2017 Annette T. Byrne, Denis G. Alférez, Frédéric Amant, Daniela Annibali, Joaquín Arribas, Andrew V. Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K. Chang, Robert B. Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S. Gail Eckhardt, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika A. Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G. Palmer, Daniel S. Peeper, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Sergio Roman-Roman, Oscar M. Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti, Livio Trusolino
Interrogating open issues in cancer precision medicine with patient-derived xenografts
published pages: 254-268, ISSN: 1474-175X, DOI: 10.1038/nrc.2016.140
Nature Reviews Cancer 17/4 2019-06-07
2017 F Mateo, E J Arenas, H Aguilar, J Serra-Musach, G Ruiz de Garibay, J Boni, M Maicas, S Du, F Iorio, C Herranz-Ors, A Islam, X Prado, A Llorente, A Petit, A Vidal, I Català, T Soler, G Venturas, A Rojo-Sebastian, H Serra, D Cuadras, I Blanco, J Lozano, F Canals, A M Sieuwerts, V de Weerd, M P Look, S Puertas, N García, A S Perkins, N Bonifaci, M Skowron, L Gómez-Baldó, V Hernández, A Martínez-Aranda, M Martínez-Iniesta, X Serrat, J Cerón, J Brunet, M P Barretina, M Gil, C Falo, A Fernández, I Morilla, S Pernas, M J Plà, X Andreu, M A Seguí, R Ballester, E Castellà, M Nellist, S Morales, J Valls, A Velasco, X Matias-Guiu, A Figueras, J V Sánchez-Mut, M Sánchez-Céspedes, A Cordero, J Gómez-Miragaya, L Palomero, A Gómez, T F Gajewski, E E W Cohen, M Jesiotr, L Bodnar, M Quintela-Fandino, N López-Bigas, R Valdés-Mas, X S Puente, F Viñals, O Casanovas, M Graupera, J Hernández-Losa, S Ramón y Cajal, L García-Alonso, J Saez-Rodriguez, M Esteller, A Sierra, N Martín-Martín, A Matheu, A Carracedo, E González-Suárez, M Nanjundan, J Cortés, C Lázaro, M D Odero, J W M Martens, G Moreno-Bueno, M H Barcellos-Hoff, A Villanueva, R R Gomis, M A Pujana
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition
published pages: 2737-2749, ISSN: 0950-9232, DOI: 10.1038/onc.2016.427
Oncogene 36/19 2019-06-07
2017 Jorge Gómez-Miragaya, Marta Palafox, Laia Paré, Guillermo Yoldi, Irene Ferrer, Sergi Vila, Patricia Galván, Pasquale Pellegrini, Hector Pérez-Montoyo, Ana Igea, Purificación Muñoz, Manel Esteller, Angel R. Nebreda, Ander Urruticoechea, Idoia Morilla, Sonia Pernas, Fina Climent, María Teresa Soler-Monso, Ana Petit, Violeta Serra, Aleix Prat, Eva González-Suárez
Resistance to Taxanes in Triple-Negative Breast Cancer Associates with the Dynamics of a CD49f+ Tumor-Initiating Population
published pages: 1392-1407, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2017.03.026
Stem Cell Reports 8/5 2019-06-07
2016 Guillermo Yoldi, Pasquale Pellegrini, Eva M. Trinidad, Alex Cordero, Jorge Gomez-Miragaya, Jordi Serra-Musach, William C. Dougall, Purificación Muñoz, Miguel-Angel Pujana, Lourdes Planelles, Eva González-Suárez
RANK Signaling Blockade Reduces Breast Cancer Recurrence by Inducing Tumor Cell Differentiation
published pages: 5857-5869, ISSN: 0008-5472, DOI: 10.1158/0008-5472.can-15-2745
Cancer Research 76/19 2019-06-07

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