PLEIO-RANK SIGNED
Pleiotropic treatment of cancer: RANK inhibitors targeting cancer stem cells and immunity
Total Cost €
0EC-Contrib. €
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Project "PLEIO-RANK" data sheet
The following table provides information about the project.
| Coordinator |
FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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 Llinà s-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 10Â 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, JoaquÃn 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 GarcÃa, A S Perkins, N Bonifaci, M Skowron, L Gómez-Baldó, V Hernández, A MartÃnez-Aranda, M MartÃnez-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 SeguÃ, 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 GarcÃa-Alonso, J Saez-Rodriguez, M Esteller, A Sierra, N MartÃn-MartÃn, 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, MarÃa 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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