INVESTIGACIÓN PRECLÍNICA
Grupo de Factores de Crecimiento

JOAQU͍N ARRIBAS

JOAQU͍N ARRIBAS
Investigador principal
Biosketch

OBJETIVOS ESTRATÉGICOS

  • Desarrollo de estrategias terapéuticas novedosas para tratar los tumores HER2 positivos e identificar mecanismos de resistencia a los tratamientos actuales.
  • Caracterización de la función de la senescencia prematura en la progresión y el tratamiento del cáncer de mama.
  • Estudio de la implicación del sistema inmunitario en la progresión del cáncer.
  • Evaluación de la actividad de estrategias terapéuticas novedosas en nuestros conjuntos de xenoinjertos derivados de pacientes de mama y páncreas.
  • Desarrollo continuado de un programa de investigación del cáncer pancreático en estrecha colaboración con el programa de investigación clínica del Instituto de Oncología Vall d’Hebron (VHIO), dirigido por Josep Tabernero.

OBJETIVOS ACTUALES

  • Desarrollar anticuerpos biespecíficos nuevos para reclutar linfocitos citotóxicos en los cánceres de mama.
  • Desarrollar modelos murinos para evaluar los tratamientos inmunitarios.
  • Diseñar nuevas estrategias para modular el fenotipo secretor de las células senescentes.
  • Identificar biomarcadores de respuesta y mecanismos de resistencia contra la inhibición de Mek en el cáncer pancreático.

COMPONENTES

Growth Factors Group
  • Investigador principal
    • Joaquín Arribas
  • Coordinador Científico
    • Cristina Bernadó
  • Médico Oncólogo
    • César Serrano
  • Becarios post-doctorales
    • Enrique Arenas
    • Beatriz Morancho
    • Mercedes Nadal
    • Bhavna Rani
    • Veronica Rodilla
  • Estudiantes graduados
    • Faiz Bilal
    • Irene Rius
  • Técnicos
    • Marta Escorihuela Baez
    • Antoni Luque
    • David Olivares
    • Jordi Rosell
    • Ismael Varela

Publicaciones científicas más relevantes

  • Morancho B, Zacarías-Fluck M, Esgueva A, Bernadó-Morales C, Di Cosimo S, Prat A, Cortés J, Arribas J, Rubio IT. Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts. Oncotarget. 2016 Oct 18;7(42):67956-67965.
  • Serra-Musach J, Mateo F, Capdevila-Busquets E, de Garibay GR, Zhang X, Guha R, Thomas CJ, Grueso J, Villanueva A, Jaeger S, Heyn H, Vizoso M, Pérez H, Cordero A, Gonzalez-Suarez E, Esteller M, Moreno-Bueno G, Tjärnberg A, Lázaro C, Serra V, Arribas J, Benson M, Gustafsson M, Ferrer M, Aloy P, Pujana MÀ. Cancer network activity associated with therapeutic response and synergism. Genome Med. 2016 Aug 24;8(1):88.
  • Hergueta-Redondo M, Sarrio D, Molina-Crespo Á, Vicario R, Bernadó-Morales C, Martínez L, Rojo-Sebastián A, Serra-Musach J, Mota A, Martínez-Ramírez Á, Castilla MÁ, González-Martin A, Pernas S, Cano A, Cortes J, Nuciforo PG, Peg V, Palacios J, Pujana MÁ, Arribas J, Moreno-Bueno G. Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer. Oncotarget. 2016 Aug 30;7(35):56295-56308.
  • Nuciforo, P., Thyparambil, S., Aura, C., Garrido-Castro, A., Marta Vilaro, M., Peg, V., Jimenez, J., Hoos, W., Burrows, J., Todd Hembrough, T., Ferreres, J. C., Perez-Garcia, J., Arribas, J., Cortes, J., and Scaltriti, M. High HER2 protein levels measured by multiplex mass spectrometry correlate with increased overall survival in patients treated with anti-HER2 therapy. Mol. Oncol. 2016 Jan;10(1):138-47.
  • Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor-Tarh D, Campbell C, Chenna A, Winslow J, Serra V, Parra JL, Prudkin L, Jimenez J, Aura C, Harbeck N, Pusztai L, Ellis C, Eidtmann H, Arribas J, Cortes J, de Azambuja E, Piccart M, Baselga J.  High HER2 expression correlates with response to the combination of lapatinib and trastuzumab.  Clin. Cancer Res. 2015 Feb; 21(3): 569-76
  • Zacarias-Fluck MF, Morancho B, Vicario R, Luque Garcia A, Escorihuela M, Villanueva J, Rubio IT, Arribas J.  Effect of cellular senescence on the growth of HER2-positive breast cancers.  J. Natl. Cancer Inst. 2015 May; 107(5)
  • Vicario R, Peg V, Morancho B, Zacarias-Fluck M, Zhang J, Martínez-Barriocanal Á, Navarro Jiménez A, Aura C, Burgues O, Lluch A, Cortes J, Nuciforo P, Rubio IT, Marangoni E, Deeds J, Boehm M, Schlegel R, Tabernero J, Mosher R, Arribas J.  Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies. PLoS ONE 2015; 10(6): e0129876
  • Massó-Vallés D, Jauset T, Serrano E, Sodir NM, Pedersen K, Affara NI, Whitfield JR, Beaulieu ME, Evan GI, Elias L, Arribas J, Soucek L.  Ibrutinib exerts potent antifibrotic and antitumor activities in mouse models of pancreatic adenocarcinoma. Cancer Res. 2015 Apr; 75(8): 1675-81
  • Morancho B, Martínez-Barriocanal Á, Villanueva J, Arribas J.  Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence. Breast Cancer Res. 2015; 17: 106
  • Pedersen K, Canals F, Prat A, Tabernero J, Arribas J.  PELO negatively regulates HER receptor signalling and metastasis. Oncogene 2014 Feb; 33(9): 1190-7
  • Gregori J, Méndez O, Katsila T, Pujals M, Salvans C, Villarreal L, Arribas J, Tabernero J, Sánchez A, Villanueva J.  Enhancing the Biological Relevance of Secretome-Based Proteomics by Linking Tumor Cell Proliferation and Protein Secretion. J. Proteome Res. 2014 Jul;
  • Parra-Palau JL, Morancho B, Peg V, Escorihuela M, Scaltriti M, Vicario R, Zacarias-Fluck M, Pedersen K, Pandiella A, Nuciforo P, Serra V, Cortes J, Baselga J, Perou CM, Prat A, Rubio IT, Arribas J.  Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy. J. Natl. Cancer Inst. 2014 Nov; 106(11)
  • García-Parra J, Dalmases A, Morancho B, Arpí O, Menendez S, Sabbaghi M, Zazo S, Chamizo C, Madoz J, Eroles P, Servitja S, Tusquets I, Yelamos J, Lluch A, Arribas J, Rojo F, Rovira A, Albanell J. Poly (ADP-ribose) polymerase inhibition enhances trastuzumab antitumour activity in HER2 overexpressing breast cancer. Eur. J. Cancer 2014 Oct; 50(15): 2725-34

Todas las publicaciones

  • Morancho B, Zacarías-Fluck M, Esgueva A, Bernadó-Morales C, Di Cosimo S, Prat A, Cortés J, Arribas J, Rubio IT. Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts. Oncotarget. 2016 Sep 1. Vol. 7, No. 42. doi: 10.18632/oncotarget.11815.
  • Hutchinson E, Pujana MA, Arribas J. Cancer therapeutic resistance: progress and perspectives. Drugs Today (Barc). 2016 Jun;52(6):347-54.
  • Serra-Musach J, Mateo F, Capdevila-Busquets E, de Garibay GR, Zhang X, Guha R, Thomas CJ, Grueso J, Villanueva A, Jaeger S, Heyn H, Vizoso M, Pérez H, Cordero A, Gonzalez-Suarez E, Esteller M, Moreno-Bueno G, Tjärnberg A, Lázaro C, Serra V, Arribas J, Benson M, Gustafsson M, Ferrer M, Aloy P, Pujana MA. Cancer network activity associated with therapeutic response and synergism. Genome Med. 2016 Aug 24;8(1):88.
  • Hergueta-Redondo M, Sarrio D, Molina-Crespo Á, Vicario R, Bernadó-Morales C, Martínez L, Rojo-Sebastián A, Serra-Musach J, Mota A, Martínez-Ramírez Á, Castilla MÁ, González-Martin A, Pernas S, Cano A, Cortes J, Nuciforo PG, Peg V, Palacios J, Pujana MÁ, Arribas J, Moreno-Bueno G. Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cáncer. Oncotarget.2016 Jul 22. Vol. 7, No. 35.
  • Esparís-Ogando A, Montero JC, Arribas J, Ocaña A, Pandiella A. Targeting the EGF/HER Ligand-Receptor System in Cancer. Curr. Pharm. Des. 2016 22(39):5887-5898.
  • Nuciforo P, Thyparambil S, Aura C, Garrido-Castro A, Marta Vilaro M, Peg V, Jimenez J, Hoos W, Burrows J, Todd Hembrough T, Ferreres JC, Perez-Garcia J, Arribas J, Cortes J, Scaltriti M. High HER2 protein levels measured by multiplex mass spectrometry correlate with increased overall survival in patients treated with anti-HER2 therapy. Mol. Oncol. 2016 Jan;10(1):138-47.
  • Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor-Tarh D, Campbell C, Chenna A, Winslow J, Serra V, Parra JL, Prudkin L, Jimenez J, Aura C, Harbeck N, Pusztai L, Ellis C, Eidtmann H, Arribas J, Cortes J, de Azambuja E, Piccart M, Baselga J.  High HER2 expression correlates with response to the combination of lapatinib and trastuzumab. Clin. Cancer Res. 2015 Feb; 21(3): 569-76
  • Zacarias-Fluck MF, Morancho B, Vicario R, Luque Garcia A, Escorihuela M, Villanueva J, Rubio IT, Arribas J.  Effect of cellular senescence on the growth of HER2-positive breast cancers. J. Natl. Cancer Inst. 2015 May; 107(5)
  • Vicario R, Peg V, Morancho B, Zacarias-Fluck M, Zhang J, Martínez-Barriocanal Á, Navarro Jiménez A, Aura C, Burgues O, Lluch A, Cortes J, Nuciforo P, Rubio IT, Marangoni E, Deeds J, Boehm M, Schlegel R, Tabernero J, Mosher R, Arribas J.  Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies. PLoS ONE 2015; 10(6): e0129876
  • Massó-Vallés D, Jauset T, Serrano E, Sodir NM, Pedersen K, Affara NI, Whitfield JR, Beaulieu ME, Evan GI, Elias L, Arribas J, Soucek L.  Ibrutinib exerts potent antifibrotic and antitumor activities in mouse models of pancreatic adenocarcinoma. Cancer Res. 2015 Apr; 75(8): 1675-81
  • Morancho B, Martínez-Barriocanal Á, Villanueva J, Arribas J.  Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence. Breast Cancer Res. 2015; 17: 106
  • Pedersen K, Canals F, Prat A, Tabernero J, Arribas J.  PELO negatively regulates HER receptor signalling and metastasis. Oncogene 2014 Feb; 33(9): 1190-7
  • Gregori J, Méndez O, Katsila T, Pujals M, Salvans C, Villarreal L, Arribas J, Tabernero J, Sánchez A, Villanueva J.  Enhancing the Biological Relevance of Secretome-Based Proteomics by Linking Tumor Cell Proliferation and Protein Secretion. J. Proteome Res. 2014 Jul;
  • Parra-Palau JL, Morancho B, Peg V, Escorihuela M, Scaltriti M, Vicario R, Zacarias-Fluck M, Pedersen K, Pandiella A, Nuciforo P, Serra V, Cortes J, Baselga J, Perou CM, Prat A, Rubio IT, Arribas J.  Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy. J. Natl. Cancer Inst. 2014 Nov; 106(11)
  • García-Parra J, Dalmases A, Morancho B, Arpí O, Menendez S, Sabbaghi M, Zazo S, Chamizo C, Madoz J, Eroles P, Servitja S, Tusquets I, Yelamos J, Lluch A, Arribas J, Rojo F, Rovira A, Albanell J. Poly (ADP-ribose) polymerase inhibition enhances trastuzumab antitumour activity in HER2 overexpressing breast cancer. Eur. J. Cancer 2014 Oct; 50(15): 2725-34
  • Morancho B, Parra-Palau JL, Ibrahim YH, Bernadó Morales C, Peg V, Bech-Serra JJ, Pandiella A, Canals F, Baselga J, Rubio I, Arribas J.  A dominant-negative N-terminal fragment of HER2 frequently expressed in breast cancers. Oncogene 2013 Mar; 32(11): 1452-9
  • Angelini PD, Zacarias Fluck MF, Pedersen K, Parra-Palau JL, Guiu M, Bernadó Morales C, Vicario R, Luque-García A, Navalpotro NP, Giralt J, Canals F, Gomis RR, Tabernero J, Baselga J, Villanueva J, Arribas J.  Constitutive HER2 signaling promotes breast cancer metastasis through cellular senescence.Cancer Res. 2013 Jan; 73(1): 450-8
  • Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratù G, Parra JL, De Mattos-Arruda L, Grueso J, Hernandez-Losa J, Arribas J, Prudkin L, Nuciforo P, Scaltriti M, Seoane J, Baselga J. Clinical response to a lapatinib-based therapy for a Li-Fraumeni syndrome patient with a novel HER2V659E mutation. Cancer Discov 2013 Nov; 3(11): 1238-44
  • Serra V, Eichhorn PJ, García-García C, Ibrahim YH, Prudkin L, Sánchez G, Rodriguez O, Anton P, Parra JL, Marlow S, Scaltriti M, Pérez-García J, Prat A, Arribas J, Hahn WC, Kim SY, Baselga J.  RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J. Clin. Invest. 2013 Jun; 123(6): 2551-63
  • Koziol A, Gonzalo P, Mota A, Pollán Á, Lorenzo C, Colomé N, Montaner D, Dopazo J, Arribas J, Canals F, Arroyo AG.  The protease MT1-MMP drives a combinatorial proteolytic program in activated endothelial cells. FASEB J. 2012 Nov; 26(11): 4481-94
  • Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, Markman B, Rodriguez O, Guzman M, Rodriguez S, Gili M, Russillo M, Parra JL, Singh S, Arribas J, Rosen N, Baselga J. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 2011 Jun; 30(22): 2547-57
  • Arribas J, Baselga J, Pedersen K, Parra-Palau JL.  p95HER2 and breast cancer. Cancer Res. 2011 Mar; 71(5): 1515-9
  • Malapeira J, Esselens C, Bech-Serra JJ, Canals F, Arribas J.  ADAM17 (TACE) regulates TGFβ signaling through the cleavage of vasorin. Oncogene 2011 Apr; 30(16): 1912-22
  • Chandarlapaty S, Scaltriti M, Angelini P, Ye Q, Guzman M, Hudis CA, Norton L, Solit DB, Arribas J, Baselga J, Rosen N.  Inhibitors of HSP90 block p95-HER2 signaling in Trastuzumab-resistant tumors and suppress their growth. Oncogene 2010 Jan; 29(3): 325-34
  • Esselens C, Malapeira J, Colomé N, Casal C, Rodríguez-Manzaneque JC, Canals F, Arribas J.  The cleavage of semaphorin 3C induced by ADAMTS1 promotes cell migration. J. Biol. Chem. 2010 Jan; 285(4): 2463-73
  • Arribas J, Parra-Palau JL, Pedersen K.  HER2 fragmentation and breast cancer stratification. Clin. Cancer Res. 2010 Aug; 16(16): 4071-3
  • Scaltriti M, Chandarlapaty S, Prudkin L, Aura C, Jimenez J, Angelini PD, Sánchez G, Guzman M, Parra JL, Ellis C, Gagnon R, Koehler M, Gomez H, Geyer C, Cameron D, Arribas J, Rosen N, Baselga J.  Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor. Clin. Cancer Res. 2010 May; 16(9): 2688-95
  • Parra-Palau JL, Pedersen K, Peg V, Scaltriti M, Angelini PD, Escorihuela M, Mancilla S, Sánchez Pla A, Ramón y Cajal S, Baselga J, Arribas J.  A major role of p95/611-CTF, a carboxy-terminal fragment of HER2, in the down-modulation of the estrogen receptor in HER2-positive breast cancers. Cancer Res. 2010 Nov; 70(21): 8537-46
  • García-Castillo J, Pedersen K, Angelini PD, Bech-Serra JJ, Colomé N, Cunningham MP, Parra-Palau JL, Canals F, Baselga J, Arribas J.  HER2 carboxyl-terminal fragments regulate cell migration and cortactin phosphorylation. J. Biol. Chem. 2009 Sep; 284(37): 25302-13
  • Pedersen K, Angelini PD, Laos S, Bach-Faig A, Cunningham MP, Ferrer-Ramón C, Luque-García A, García-Castillo J, Parra-Palau JL, Scaltriti M, Ramón y Cajal S, Baselga J, Arribas J.  A naturally occurring HER2 carboxy-terminal fragment promotes mammary tumor growth and metastasis. Mol. Cell. Biol. 2009 Jun; 29(12): 3319-31
  • Scaltriti M, Verma C, Guzman M, Jimenez J, Parra JL, Pedersen K, Smith DJ, Landolfi S, Ramón y Cajal S, Arribas J, Baselga J.  Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene 2009 Feb; 28(6): 803-14
  • Arribas J, Esselens C.  ADAM17 as a therapeutic target in multiple diseases. Curr. Pharm. Des. 2009; 15(20): 2319-35
  • Baselga J, Scaltriti M, Rojo F, Ocaña A, Anido J, Guzman M, Cortes J, Di Cosimo S, Matias-Guiu X, Ramón y Cajal S, Arribas J.  Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J. Natl. Cancer Inst. 2007 Apr; 99(8): 628-38
  • Anido J, Scaltriti M, Bech Serra JJ, Santiago Josefat B, Todo FR, Baselga J, Arribas J.  Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J. 2006 Jul; 25(13): 3234-44
  • Bech-Serra JJ, Santiago-Josefat B, Esselens C, Saftig P, Baselga J, Arribas J, Canals F.  Proteomic identification of desmoglein 2 and activated leukocyte cell adhesion molecule as substrates of ADAM17 and ADAM10 by difference gel electrophoresis. Mol. Cell. Biol. 2006 Jul; 26(13): 5086-95
  • Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J.  TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J. 2003 Mar; 22(5): 1114-24