CFAH GRUP DE FACTORS DEL CREIXEMENT – VHIO – Vall d'Hebron Institute of Oncology

GRUP DE FACTORS DEL CREIXEMENT

RECERCA PRECLÍNICA I TRANSLACIONAL
Grup de Factors del Creixement

JOAQU͍N ARRIBAS
Investigador principal
Biosketch

Continuem la nostra línia d’investigació sobre noves immunoteràpies mitjançant la generació de nous CAR (receptors d’antígens quimèrics). Amb el coneixement acumulat durant el desenvolupament i la caracterització d’anticossos biespecífics, hem pogut desenvolupar de manera eficient els nostres CAR, que es dirigeixen contra la proteïna p95HER2, només present en alguns tumors mamaris i gàstrics, i completament absent en els teixits normals. És important destacar que aquest projecte ha estat finançat per l’Associació Espanyola Contra el Càncer (AECC) durant els propers cinc anys.

A més, la nostra plataforma de models experimentals derivats de pacients amb càncer de mama i de pàncrees, en constant expansió, ens va portar a establir diverses col·laboracions fructíferes amb diversos grups nacionals i internacionals. Aquestes aliances ens han permès identificar nous mecanismes de resistència a les teràpies contra el càncer (Lambies et al., Diaz-Rodriguez et al. I Gomez-Miragaya et al.), Així com biomarcadors de sensibilitat a medicaments de precisió (Kang et a l’ . i Blasco-Benito et al.).

El nostre grup també ha contribuït a la caracterització d’un nou conjugat de fàrmac i anticòs que és eficaç contra alguns tumors pancreàtics i càncers de mama triple negatius (Merlino et al.). Finalment, també hem col·laborat en la identificació de fàrmacs dirigits a cèl·lules senescents que, en determinades circumstàncies, contribueixen de forma important a la progressió tumoral. Al VHIO, hem treballat amb diversos grups en una investigació dirigida per Sandra Peiró, investigadora principal del nostre Grup de Dinàmica de la Cromatina en el Càncer, per revelar els mecanismes que regulen l’expressió gènica en el càncer de mama triple negatiu (Cebria Costa et al.).

El nostre enfocament altament col·laboratiu també ens ha permès participar en diversos projectes a gran escala finançats per la Unió Europea aquest any, inclòs el projecte Immune-Image, el suport de la Iniciativa de Medicaments Innovadors (IMI). Aquest consorci a gran escala té com a objectiu desenvolupar traçadors nous per controlar la resposta immunitària a les teràpies antitumorals per a la investigació de xenoempelts de càncer derivats de pacients. També vam participar en el projecte multicèntric COLOSSUS amb el suport d’Horitzó 2020 de la Comissió Europea (Avanç d’un paradigma de medicina de precisió en el càncer colorectal metastàtic: sistemes basats en solucions d’estratificació de pacients), per al qual el nostre grup està desenvolupant models murins humanitzats.

També s’ha d’esmentar el continu suport i suport rebut de la Breast Cancer Research Foundation (BCRF), a la qual estem summament agraïts.

OBJECTIUS ESTRATÈGICS

  • Generació i caracterització de CAR davant d’un subconjunt de tumors positius per a HER2.
  • Desenvolupar un ADC contra p95HER2.
  • Determinar la funció de la senescència cel·lular en la progressió i el tractament del càncer de mama.
  • Identificar nous mecanismes de resistència als tractaments dirigits contra el càncer de pàncrees.

ASPECTES DESTACATS

  • Hem iniciat el desenvolupament d’una nova teràpia basada en limfòcits T contra el càncer de mama p95HER2 positiu, p95HER2-CAR.
  • El nostre grup ha caracteritzat mecanismes de resistència enfront de teràpies anti-HER2 en el càncer de mama.
  • Hem identificat nous factors implicats en la resistència de el càncer de pàncrees als inhibidors de MEK.
  • Hem col·laborat en la caracterització de nous compostos senolítics.

EQUIP

  • Investigador principal
    • Joaquín Arribas
  • Becaris postdoctorals
    • Enrique Arenas
    • Cristina Bernadó
    • Beatriz Morancho
    • Irene Rius
    • Verónica Rodilla
  • Estudiants llicenciats
    • Luis Alfonso Garcia
    • Alejandro Martínez-Sabadell
    • Macarena Román Alonso
  • Estudiants
    • Jose Angel Palomeque
    • Daniel Fernando Pilco
    • Carlos Ramirez
    • Federica Zanotti
  •  Tècnics
    • Marta Escorihuela
    • Antonio Miguel Luque

 


Publicacions científiques més rellevants

  • Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, Soprano E, Pedrosa P, Ferreirós A, Barradas M, Hernández-González F, Lalinde M, Prats N, Bernadó C, González P, Gómez M, Ikonomopoulou MP, Fernández-Marcos PJ, García-Caballero T, Del Pino P, Arribas J, Vidal A, González-Barcia M, Serrano M, Loza MI, Domínguez E, Collado M. Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat. Commun. 2019 Oct 21;10(1):4731.
  • Blasco-Benito S, Moreno E, Seijo-Vila M, Tundidor I, Andradas C, Caffarel MM, Caro-Villalobos M, Urigüen L, Diez-Alarcia R, Moreno-Bueno G, Hernández L, Manso L, Homar-Ruano P, McCormick PJ, Bibic L, Bernadó Morales C, Arribas J, Canals M, Casadó V, Canela EI, Guzmán M, Pérez-Gómez E, Sánchez C. Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer. Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3863-3872.
  • Kang SA, Guan JS, Tan HJ, Chu T, Thike AA, Bernadó Morales C, Arribas J, Wong CY, Tan PH, Gudi M, Putti TC, Sohn J, Lim SH, Lee SC, Lim YP. Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab-based neo-adjuvant therapy:A Retrospective and Multicentric Study. Clin. Cancer Res. 2019 Apr 15;25(8):2588-2600.
  • Lambies G, Miceli M, Martínez-Guillamon C, Olivera-Salguero R, Peña R, Frías CP, Calderón I, Atanassov BS, Dent SYR, Arribas J, García de Herreros A, Díaz VM. TGFβ-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. Cancer Res. 2019 Jan 1;79(1):33-46.
  • Rius Ruiz I et al, p95HER2-T Cell Bispecific Antibody for Breast Cancer Treatment. Sci Transl Med.  03 Oct 2018: Vol. 10, Issue 461, eaat1445. DOI: 10.1126/scitranslmed.aat1445. To access the full text of this paper visit: http://stm.sciencemag.org/cgi/content/full/10/461/eaat1445?ijkey=2KMN994dBpkGI&keytype=ref&siteid=scitransmed
  • Méndez, O. Peg , V., Salvans, C., Pujals, M., Fernández, Y.,Abasolo, I.,Pérez, J.,Matres, A.,Valeri. ,Gregori, J.,Villarreal, J.,Schwartz Jr, S.,Ramon y Cajal, S.,Tabernero, J.,Cortés, J., Arribas, J.,Villanueva, J. Extracellular HMGA1 promotes Triple-Negative Breast Cancer Invasion and Metastasis by regulating tumor cell adhesion through RAGE signalling (2018) Clin Cancer Res 24, 6367-6382.
  • Cruz, C., Llop-Guevara, A., E. Garber, J. E., Arun, B. K., Pérez Fidalgo, J. A., Lluch, A., Telli, M. L., Fernández, C., Kahatt, C., Galmarini, C. M., Soto-Matos, A., Alfaro, V., Pérez de la Haza, A., Domcheck, S. M., Antolin, S., Vahdat, L., Tung, N. M., Lopez, R., Arribas, J., Vivancos, A., Baselga, J., Serra, V., Balmaña, J. & Isakoff, S. J. (2018) Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Sub-study (2018) J Clin Oncol 36, 3134-3143.
  • Georgilis, A., Klotz, S., Hanley, C. J., Herranz, N., Weirich, B., Morancho, B., Leote, A. C., D’Artista, L., Gallage, S., Seehawer, M., Carroll, T., Dharmalingam, G., Keng Boon, D. W, Mellone, M., Pombo, J., Heide, D., Guccione, E. ., Arribas, J., Barbosa-Morais, N. L., Heikenwalder, M., Thomas, G. J., Zender, L. and  Gil, J. PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells (2018) Cancer Cell 34, 85-102.
  • Serrano-Candelas, E., Ainsua-Enrich, E., Navinés-Ferrer, A., Rodrigues, P., García-Valverde, A., Bazzocco, S., Macaya, I., Arribas, J., Serrano, C., Sayós, J., Arango., D. and Martin, M. (2018) Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth (2018) Molecular Oncology 12, 1383–1397.
  • Serrano, C., García-del-Muro, X., Valverde, C., Sebio, A., Durán, J., Manzano, A., Pajares, I., Hindi, N., Landolfi, S., Jiménez, L., Rubió-Casadevall, J., Estival, A., Lavernia, J., Safont, M. J., Pericay, C., Díaz-Beveridge, R., Martínez-Marín, V., Vicente-Baz, D., Vivancos, A., Hernández-Losa, J., Arribas, J.*, Carles, J.* (2018) Clinicopathological and molecular characterization of metastatic gastrointestinal stromal tumors patients with prolonged benefit to frontline imatinib. Oncologist 2018 Aug 20. pii: theoncologist.2018-0032
  • Cruz, C., Castroviejo-Bermejo, M., Gutiérrez-Enríquez, S., Llop-Guevara, A., Ibrahim, Y. H., Gris-Oliver A., Bonache, S., Morancho, B., Bruna, A., Rueda, O. M. , Lai, Z., Polanska, U. M., Jones, G. N., Kristel, P., de Bustos, L., Guzman, M., Rodriguez, O., Grueso, J., Montalban, G., Caratú, G., Mancuso, F., Fasani, R., Jiménez, J., Howat, W. J., Dougherty, B., Vivancos, A., Nuciforo, P., Serres-Créixams, X., Rubio, I. T., Oaknin, A., Cadogan, E., Barrett, J. C., Caldas, C., Baselga, J., Saura, C., Cortés, J., Arribas, J., Jonkers, J., Díez, O., O’Connor, M. J., Balmaña, J., Serra, V. (2018) RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA mutated breast cancer. Ann Oncol 29, 1203-1210.
  • Floros, K., Lochmann, T., Bin Hu, B., Monterrubio, C., Hughes, H., Wells, J., Bernadó Morales, C., Ghotra, M., Harada, H., Costa, C., Souers, A., Leverson, J., Tan, M., Serra, V., Koblinski, J., Arribas, J., Miller, T., Dozmorov, M., Windle, B., Scaltriti, M. and Faber, A (2018) Co-amplification of miR-4728 protects HER2-amplified breast cancers from targeted therapy. Proc Natl Acad Sci 115:E2594-E2603.
  • Gawrzak, S., Rinaldi, L., Arenas, E. J., Salvador, F., Gregorio, S., Rojo, F., del Barco Barrantes, I., Cejalvo, J. M., Palafox, M., Guiu, M. , Berenguer-Llergo, A., Symeonidi, A., Urosevic, J., Bellmunt, A., Kalafatovic, D., Arnal-Estapé, A., Fernández, E., Müllauer, B., Groeneveld, R., Slobodnyuk, K., Stephan-Otto Attolini, C., Saura, C., Arribas, J.,  Cortes, J., Ana Rovira, A., , Muñoz, M., Lluch, A., , Serra, V., Albanell, J.,  Prat, A.,  Nebreda, A. R., Aznar-Benitah, S. & Gomis, R. R. (2018) MSK1 regulates luminal cell differentiation and metastatic dormancy in breast cancer Nature Cell Biol 20, 211-221.
  • Ríos-Luci C, García-Alonso S, Díaz-Rodríguez E, Nadal-Serrano M, Arribas J, Ocaña A, Pandiella A. Resistance to the Antibody-Drug Conjugate T-DM1 Is Based in a Reduction in Lysosomal Proteolytic Activity. Cancer Res. 2017 Sep 1;77(17):4639-4651.
  • Sabbaghi M, Gil-Gómez G, Guardia C, Servitja S, Arpí O, García-Alonso S, Menendez S, Arumi-Uria M, Serrano L, Salido M, Muntasell A, Martínez-García M, Zazo S, Chamizo C, González-Alonso P, Madoz-Gúrpide J, Eroles P, Arribas J, Tusquets I, Lluch A, Pandiella A, Rojo F, Rovira A, Albanell J. Defective Cyclin B1 Induction in Trastuzumab-emtansine (T-DM1) Acquired Resistance in HER2-positive Breast Cancer. Clin Cancer Res. 2017 Nov 15;23(22):7006-7019.
  • Pedersen K, Bilal F, Bernadó Morales C, Salcedo MT, Macarulla T, Massó-Vallés D, Mohan V, Vivancos A, Carreras MJ, Serres X, Abu-Suboh M, Balsells J, Allende E, Sagi I, Soucek L, Tabernero J, Arribas J. Pancreatic cancer heterogeneity and response to Mek inhibition. Oncogene. 2017 Oct 5;36(40):5639-5647.
  • Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinská E, Caldas C, Chang DK, Clarke RB, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek MA, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer HG, Peeper DS, Pelicci PG, Piris-Gimenez A, Roman-Roman S, Rueda OM, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Cancer. 2017 Apr;17(4):254-268.
  • 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

Totes les publicacions

  • Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, Soprano E, Pedrosa P, Ferreirós A, Barradas M, Hernández-González F, Lalinde M, Prats N, Bernadó C, González P, Gómez M, Ikonomopoulou MP, Fernández-Marcos PJ, García-Caballero T, Del Pino P, Arribas J, Vidal A, González-Barcia M, Serrano M, Loza MI, Domínguez E, Collado M. Identification and characterization of Cardiac Glycosides as senolytic compounds. (2019) Nat Commun. 10(1):4731. doi: 10.1038/s41467-019-12888-x.
  • Cebrià-Costa , J. P., Pascual-Reguant, L., Gonzalez-Pérez ,A., Serra-Bardenys , G., Querol , J., Cosin, M., Verde, G., Cigliano, RA., Sanseverino, W., Segura-Bayona S, Iturbide A, Andreu , D., Nuciforo, P., Bernadó-Morales, C.,  Rodilla V, Arribas, J., Yelamos J, de Herreros, A.G, Stracker TH, Peiró S. LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple negative breast cancer cells.  (2019) Oncogene. 2019 Aug 28. doi: 10.1038/s41388-019-0969-1.
  • Gomez-Miragaya, J., Díaz-Navarro, A., Tonda, R., Beltran, S., Palomero, L., Palafox, M., Dobrolecki, L., Vasaikar, S., Huang, C., Zhang, B., Wulf, G., Muñoz, P., Paré, L., Serra, V., Prat, A., Bruna, A., Caldas, C., Arribas, J., Balmaña, J., Cruz, C., Pujana, M. A., Lewis, M., Puente, X., Gonzalez-Suarez, E. Chromosome 12p amplification in triple-negative breast cancer is associated with emergent docetaxel resistance and carboplatin sensitivity (2019) Cancer Research79, 4258-4270.
  • Merlino, G., Fiascarelli, A., Bigioni, M., Bressan, A., Carrisi, C., Bellarosa, D., Salerno, M., Bugianesi, R., Manno, R., Bernadó Morales, C., Arribas, J., Dusek, R. L., Pham, P. H., Awdew, R., Aud, D. M., Trang, M., Terrett, J., Wilson, K. E., Rohlff, C., Manzin, S., Pellacani, A, Binaschi, M. MEN1309/OBT076, a first-in-class Antibody Drug Conjugate (ADC) targeting CD205 in solid tumors (2019) Mol Cancer Ther. 2019 Sep;18(9):1533-1543.
  • Diaz-Rodriguez, E., Pérez-Peña, J., Ríos-Luci, C., Arribas, J., Ocaña, A., Pandiella, A. TRAIL receptor activation overcomes resistance to trastuzumab in HER2 positive breast cancer cells (2019) Cancer Letters 453, 34-44.
  • Gorbatenko, A., Søkilde, R., Sorensen, E. E., Newie, I., Persson, H., Morancho, B., Arribas, J., Litman, T., Rovira, C., Pedersen, S. F. HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503 (2019) Scientific Reports 9, 3352.
  • Blasco-Benito S, Moreno E, Seijo-Vila M, Tundidor I, Andradas C, Caffarel MM, Caro-Villalobos M, Urigüen L, Diez-Alarcia R, Moreno-Bueno G, Hernández L, Manso L, Homar-Ruano P, McCormick PJ, Bibic L, Bernadó Morales C, Arribas J, Canals M, Casadó V, Canela EI, Guzmán M, Pérez-Gómez E, Sánchez C. Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer. (2019) Proc Natl Acad Sci U S A. 116(9) 3863-3872.
  • Kang SA, Guan JS, Tan HJ, Chu T, Thike AA, Bernadó Morales C, Arribas J, Wong CY, Tan PH, Gudi M, Putti TC, Sohn J, Lim SH, Lee SC, Lim YP. Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab-based neo-adjuvant therapy:A Retrospective and Multicentric Study. Clin Cancer Res. 2019 Apr 15;25(8):2588-2600.
  • Lambies G, Miceli M, Martínez-Guillamon C, Olivera-Salguero R, Peña R, Frías CP, Calderón I, Atanassov BS, Dent SYR, Arribas J, García de Herreros A, Díaz VM. TGFβ-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. (2019) Cancer Res. 2019 Jan 1. 79(1):33-46.
  • Gawrzak S, Rinaldi L, Gregorio S, Arenas EJ, Salvador F, Urosevic J, Figueras-Puig C, Rojo F, Del Barco Barrantes I, Cejalvo JM, Palafox M, Guiu M, Berenguer-Llergo A, Symeonidi A, Bellmunt A, Kalafatovic D, Arnal-Estapé A, Fernández E, Müllauer B, Groeneveld R, Slobodnyuk K, Stephan-Otto Attolini C, Saura C, Arribas J, Cortes J, Rovira A, Muñoz M, Lluch A, Serra V, Albanell J, Prat A, Nebreda AR, Benitah SA, Gomis RR. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nat Cell Biol. 2018 Jan 22. doi: 10.1038/s41556-017-0021-z. [Epub ahead of print]
  • Martín-Pérez, R., Yerbes, R., Mora-Molina, R., Cano- González, A., Arribas, J., Mazzone, M., López- Rivas, A.  and Palacios, C. Oncogenic p95HER2/611CTF primes human breast epithelial cells for metabolic stress-induced down-regulation of FLIP and activation of TRAIL-R/Caspase-8-dependent apoptosis.  2017. Oct 3;8(55):93688-93703. doi: 10.18632/oncotarget.21458. eCollection 2017 Nov 7.
  • Ríos-Luci, C., García-Alonso S., Díaz-Rodríguez E., Nadal-Serrano, M., Arribas, J., Ocaña, A. and Pandiella, A. Deficient lysosomal proteolytic activity underlies resistance to the antibody-drug conjugate trastuzumab-emtansine. Cancer Res Sep 1;77(17):4639-4651. doi: 10.1158/0008-5472.CAN-16-3127. Epub 2017 Jul 7.
  • Sabbaghi M, Gil-Gómez G, Guardia C, Servitja S, Arpí O, García-Alonso S, Menendez S, Arumi-Uria M, Serrano L, Salido M, Muntasell A, Martínez-García M, Zazo S, Chamizo C, González-Alonso P, Madoz-Gúrpide J, Eroles P, Arribas J, Tusquets I, Lluch A, Pandiella A, Rojo F, Rovira A, Albanell J. Defective Cyclin B1 Induction in Trastuzumab-emtansine (T-DM1) Acquired Resistance in HER2-positive Breast Cancer. Clin Cancer Res. 2017 Nov 15. 23(22):7006-7019. doi: 10.1158/1078-0432.CCR-17-0696. Epub 2017 Aug 18.
  • Pedersen, K.*, Bilal, F.*, Bernadó Morales, C., Salcedo, MT., Macarulla, T., Massó-Vallés, D., Mohan, V., Vivancos, V., Carreras, MJ., Serres, X., Abu-Suboh, M., Balsells, J., Allende, E., Sagi, I., Soucek, L., Tabernero, J., Arribas, J. Pancreatic cancer heterogeneity and response to Mek inhibition. Oncogene, 2017. Oct 5;36(40):5639-5647. doi: 10.1038/onc.2017.174. Epub 2017 Jun 5.
  • Byrne, A. T., Alférez, A. G.,Amant, F., Annibali, D., Arribas, J., Biankin, A. V., Bruna, A., Budinská, E., Caldas, C., Chang, D. K., Clarke, R. B., Clevers, H., Coukos, G., Dangles-Marie, V., Eckhardt, S. G. , Gonzalez-Suarez, E. G. , Els Hermans, E, Hidalgo, M., Jarzabek, M., de Jong, S., Jonkers, J., Kemper, K., Lanfrancone, L., Mælandsmo, G. M., Marangoni, E., Marine, J.-C., Enzo Medico, E., Norum, J. H., Palmer, H. G., Peeper, D. S.,Pelicci, P.G., Piris, A., Roman-Roman, S., Rueda, O. M., Seoane, J., Serra, V., Soucek, L., Vanhecke, D., Villanueva, A., Vinolo, E., Bertotti, A., Trusolino, L. (2017) Interrogating open issues in cancer precision medicine with Patient-Derived Xenografts. Nature Rev CancerSep 15;17(10):632. doi: 10.1038/nrc.2017.85. [Epub ahead of print]
  • 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