We focus our research on mechanisms of resistance to targeted therapies and most importantly, how to overcome it by showing that breast cancers resistant to T-DM1, an antibody-drug conjugate ADC)- can be efficiently treated with the second generation ADC SYD985 (Nadal-Serrano et al.).
Our group has also contributed to determining the clinical value of plasma cell-free DNA and the efficacy of PI3K inhibition in gastrointestinal tumors and (Serrano et al; García-Valverde et al.). Finally, we have collaborated in a position paper on how to enhance global access to cancer medicines (Cortes el al.)
In addition, our ever-expanding platform of breast and pancreatic cancer patient-derived experimental models has enabled us to establish several fruitful collaborations with other groups at VHIO. We have collaborated in the characterization of the genetic abnormalities that determine sensitivity to Akt inhibitors (Gris-Oliver et al.), and in defining how epigenetic changes regulate the accessibility of chromatin in triple negative breast cancer (Cebrià-Costa el al.).
In parallel, we have continued our research into novel immune therapies by generating novel CARs (chimeric antigen receptors). With the knowledge accumulated during the development and characterization of bispecific antibodies, we have been able to efficiently develop our CARS that are directed against the p95HER2 protein; only present in some mammary and gastric tumors, and completely absent in normal tissues. Importantly, this project has been funded by the Spanish Association against Cancer (AECC) for the next five years.
Mention must also be made regarding the continued backing and support received from the Breast Cancer Research Foundation (BCRF), for which we are extremely grateful.
- Generation and characterization of CARs against tumor specific antigens.
- Determine the role of cellular senescence in breast cancer progression and treatment.
- Identification of new mechanisms of resistance to targeted therapies.
Group Leader
Joaquín Arribas
Post-Doctoral Fellows
Enrique Javier Arenas
Vanesa Nogales
Graduate Students
Ariadna Grinyó
Macarena Román Alonso
Marta Lalinde
Pablo Ovejero
Technicians
Marta Escorihuela
Sandra Perez
Judith Gago
Visiting scientists
Alex Martínez-Sabadell
Marta Bort
Constanza Cortes,
Santiago Duro
Christopher George
Most relevant scientific publications
- Pascual-Reguant L, Serra-Camprubí Q, Datta D, Cianferoni D, Kourtis S, Gañez-Zapater A, Cannatá C, Espinar L, Querol J, García-López L, Musa-Afaneh S, Guirola M, Gkanogiannis A, Miró Canturri A, Guzman M, Rodríguez O, Herencia-Ropero A, Arribas J, Serra V, Serrano L, Tian TV, Peiró S, Sdelci S. Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer. EMBO Mol Med. 2023 Dec 7;15(12):e18459.
- Serra-Camprubí Q, Verdaguer H, Oliveros W, Lupión-Garcia N, Llop-Guevara A, Molina C, Vila-Casadesús M, Turpin A, Neuzillet C, Frigola J, Querol J, Yáñez-Bartolomé M, Castet F, Fabregat-Franco C, Escudero-Iriarte C, Escorihuela M, Arenas EJ, Bernadó-Morales C, Haro N, Giles FJ, Pozo ÓJ, Miquel JM, Nuciforo PG, Vivancos A, Melé M, Serra V, Arribas J, Tabernero J, Peiró S, Macarulla T, Tian TV. Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation. Clin Cancer Res. 2023 Jan 17;29(2):432-445.
- Pérez Del Río E, Román Alonso M, Rius I, Santos F, Castellote-Borrell M, Veciana J, Ratera I, Arribas J, Guasch J. Three-dimensional cell culture of chimeric antigen receptor T cells originated from peripheral blood mononuclear cells towards cellular therapies. Cytotherapy. 2023 Dec;25(12):1293-1299.
- Quintana Á, Arenas EJ, Bernadó C, Navarro JF, González J, Esteve-Codina A, Moliné T, Marti M, Curigliano G, Schmid P, Peg V, Arribas J, Cortés J. Evaluation of triple negative breast cancer with heterogeneous immune infiltration. Front Immunol. 2023 May 4;14:1149747.
- Duro-Sánchez S, Nadal-Serrano M, Lalinde-Gutiérrez M, Arenas EJ, Bernadó Morales C, Morancho B, Escorihuela M, Pérez-Ramos S, Escrivá-de-Romaní S, Gandullo-Sánchez L, Pandiella A, Esteve-Codina A, Rodilla V, Dijcks FA, Dokter WHA, Cortés J, Saura C, Arribas J. Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody-Drug Conjugates in Breast Cancer. Cancer Res. 2022 Dec 16;82(24):4670-4679.
- Martínez-Sabadell A, Morancho B, Rius Ruiz I, Román Alonso M, Ovejero Romero P, Escorihuela M, Chicote I, Palmer HG, Nonell L, Alemany-Chavarria M, Klein C, Bacac M, Arribas J, Arenas EJ. The target antigen determines the mechanism of acquired resistance to T cell-based therapies. Cell Rep. 2022 Oct 18;41(3):111430.
- Martínez-Sabadell A, Arenas EJ, Arribas J. IFNγ Signaling in Natural and Therapy-Induced Antitumor Responses. Clin Cancer Res. 2022 Apr 1;28(7):1243-1249.
- Adam-Artigues A, Arenas EJ, Martínez-Sabadell A, Brasó-Maristany F, Cervera R, Tormo E, Hernando C, Martínez MT, Carbonell-Asins J, Simón S, Poveda J, Moragón S, Zazo S, Martínez D, Rovira A, Burgués O, Rojo F, Albanell J, Bermejo B, Lluch A, Prat A, Arribas J, Eroles P, Cejalvo JM. Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer. Sci Adv. 2022 May 20;8(20):eabk2746.
- Bilal, F., Arenas, E. J., Pedersen, K., Martínez-Sabadell, A., Nabet, B., Guruceaga, E., Vicent, S., Tabernero, J., Macarulla, T. and Arribas, J. The transcription factor Slug uncouples pancreatic cancer progression from the Raf-Mek1/2-Erk1/2 pathway (2021) Cancer Research, accepted
- Arenas, E. J., Martínez-Sabadell, A., Rius Ruiz, I., Román Alonso, M., Escorihuela, M., Luque, A., Fajardo, C. A, Gros, A., Klein, C. Arribas, J. Resistance to HER2-TCB (T cell bispecfic) and -CAR (chimeric antigen receptor) through JAK2 downmodulation (2021). Nature Comm, 12, 1237
- Cortes J, Perez-García JM, Llombart-Cussac A, Curigliano G, El Saghir NS, Cardoso F, Barrios CH, Wagle S, Roman J, Harbeck N, Eniu A, Kaufman PA, Tabernero J, García-Estévez L, Schmid P, Arribas J. Enhancing global access to cancer medicines. CA Cancer J Clin. 2020 Mar;70(2):105-124.
- Serrano C, Vivancos A, López-Pousa A, Matito J, Mancuso FM, Valverde C, Quiroga S, Landolfi S, Castro S, Dopazo C, Sebio A, Virgili AC, Menso MM, Martín-Broto J, Sansó M, García- Valverde A, Rosell J, Fletcher JA, George S, Carles J, Arribas J. Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors. BMC Cancer. 2020 Feb 5;20(1):99.
- Rius Ruiz I*, Vicario R*, Morancho B, Bernadó Morales C, Arenas EJ, Herter S, Freimoser-Grundschober A, Somandin J, Sam J, Ast O, Martínez Barriocanal Á, Luque A, Escorihuela M, Varela I, Cuartas I, Nuciforo P, Fasani R, Peg V, Rubio I, Cortés J, Serra V, Escriva-de-Romani S, Sperinde J, Chenna A, Huang W, Winslow J, Albanell J, Seoane J, Scaltriti M, Baselga J, Tabernero J, Umana P, Bacac M, Saura C†, Klein C†, Arribas J†, ‡. p95HER2-T cell bispecific antibody for breast cancer treatment. Sci Transl Med 10(461) pii: eaat1445 (2018)
- Morancho, B.*, Martínez-Barriocanal, A.*, Villanueva, J. and Arribas, J‡. Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence. Breast Cancer Res 17, 106 (2015)
- Zacarias-Fluck, M., Morancho, B., Vicario, R., Luque-García, A., Escorihuela, M., Villanueva, J., Rubio, I. & Arribas, J. Effect of Cellular Senescence on the Growth of HER2-positive breast cancers. J Natl Cancer Inst 107 (5): djv020 (2015)
- 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
- 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
- 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)
All publications
- Fiascarelli, A., Merlino, G., Capano, S., Talucci, S., Bisignano, D., Bressan, A., Bellarosa, D., Carrisi, C., Paoli, A., Bigioni, M., et al. (2023). Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer. Breast Cancer Res. Treat. 199, 13–23. 10.1007/s10549-023-06895-2.
- Pascual‐Reguant, L., Serra‐Camprubí, Q., Datta, D., Cianferoni, D., Kourtis, S., Gañez‐Zapater, A., Cannatá, C., Espinar, L., Querol, J., García‐López, L., et al. (2023). Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple‐negative breast cancer. EMBO Mol. Med. 15, e18459. 10.15252/emmm.202318459.
- Serra-Camprubí, Q., Verdaguer, H., Oliveros, W., Lupión-Garcia, N., Llop-Guevara, A., Molina, C., Vila-Casadesús, M., Turpin, A., Neuzillet, C., Frigola, J., et al. (2023). Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation. Clin. Cancer Res. 29, 432–445. 10.1158/1078-0432.ccr-22-2551.
- Río, E.P. del, Alonso, M.R., Rius, I., Santos, F., Castellote-Borrell, M., Veciana, J., Ratera, I., Arribas, J., and Guasch, J. (2023). Three-dimensional cell culture of chimeric antigen receptor T cells originated from peripheral blood mononuclear cells towards cellular therapies. Cytotherapy 25, 1293–1299. 10.1016/j.jcyt.2023.08.003.
- Quintana, Á., Arenas, E.J., Bernadó, C., Navarro, J.F., González, J., Esteve-Codina, A., Moliné, T., Marti, M., Curigliano, G., Schmid, P., et al. (2023). Evaluation of triple negative breast cancer with heterogeneous immune infiltration. Front. Immunol. 14, 1149747. 10.3389/fimmu.2023.1149747.
- Duro-Sánchez, S., Alonso, M.R., and Arribas, J. (2023). Immunotherapies against HER2-Positive Breast Cancer. Cancers 15, 1069. 10.3390/cancers15041069.
- 7. Adam-Artigues, A., Arenas, E.J., Arribas, J., Prat, A., and Cejalvo, J.M. (2023). AXL – a new player in resistance to HER2 blockade. Cancer Treat. Rev. 121, 102639. 10.1016/j.ctrv.2023.102639.
- Saura, C., Ortiz, C., Matito, J., Arenas, E.J., Suñol, A., Martín, Á., Córdoba, O., Martínez-Sabadell, A., García-Ruiz, I., Miranda, I., et al. (2023). Early-Stage Breast Cancer Detection in Breast Milk. Cancer Discov. 13, OF1–OF12. 10.1158/2159-8290.cd-22-1340.
- Pérez-Núñez I, Rozalén C, Palomeque JÁ, Sangrador I, Dalmau M, Comerma L, Hernández-Prat A, Casadevall D, Menendez S, Liu DD, Shen M, Berenguer J, Ruiz IR, Peña R, Montañés JC, Albà MM, Bonnin S, Ponomarenko J, Gomis RR, Cejalvo JM, Servitja S, Marzese DM, Morey L, Voorwerk L, Arribas J, Bermejo B, Kok M, Pusztai L, Kang Y, Albanell J, Celià-Terrassa T. LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer. Nat Cancer . 2022 Mar;3(3):355-370. doi: 10.1038/s43018-022-00339-4. Epub 2022 Mar 17. PMID: 35301507.
- Adam-Artigues A, Arenas EJ, Martínez-Sabadell A, Brasó-Maristany F, Cervera R, Tormo E, Hernando C, Martínez MT, Carbonell-Asins J, Simón S, Poveda J, Moragón S, Zazo S, Martínez D, Rovira A, Burgués O, Rojo F, Albanell J, Bermejo B, Lluch A, Prat A, Arribas J, Eroles P, Cejalvo JM. Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer. Sci Adv . 2022 May 20;8(20):eabk2746. doi: 10.1126/sciadv.abk2746. Epub 2022 May 20. PMID: 35594351; PMCID: PMC9122332.
- Pellegrino B, Herencia-Ropero A, Llop-Guevara A, Pedretti F, Moles-Fernández A, Viaplana C, Villacampa G, Guzmán M, Rodríguez O, Grueso J, Jiménez J, Arenas EJ, Degasperi A, Dias JML, Forment JV, O’Connor MJ, Déas O, Cairo S, Zhou Y, Musolino A, Caldas C, Nik-Zainal S, Clarke RB, Nuciforo P, Díez O, Serres-Créixams X, Peg V, Espinosa-Bravo M, Macarulla T, Oaknin A, Mateo J, Arribas J, Dienstmann R, Bellet M, Oliveira M, Saura C, Gutiérrez-Enríquez S, Balmaña J, Serra V. Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification. Cancer Res . 2022 Apr 15;82(8):1646-1657. doi: 10.1158/0008-5472.CAN-21-2409. PMID: 35425960; PMCID: PMC7612637.
- Serra V, Wang AT, Castroviejo-Bermejo M, Polanska UM, Palafox M, Herencia-Ropero A, Jones GN, Lai Z, Armenia J, Michopoulos F, Llop-Guevara A, Brough R, Gulati A, Pettitt SJ, Bulusu KC, Nikkilä J, Wilson Z, Hughes A, Wijnhoven PWG, Ahmed A, Bruna A, Gris-Oliver A, Guzman M, Rodríguez O, Grueso J, Arribas J, Cortés J, Saura C, Lau A, Critchlow S, Dougherty B, Caldas C, Mills GB, Barrett JC, Forment JV, Cadogan E, Lord CJ, Cruz C, Balmaña J, O’Connor MJ. Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance. Clin Cancer Res . 2022 Oct 14;28(20):4536-4550. doi: 10.1158/1078-0432.CCR-22-0568. PMID: 35921524; PMCID: PMC9561606.
- Palafox M, Monserrat L, Bellet M, Villacampa G, Gonzalez-Perez A, Oliveira M, Brasó-Maristany F, Ibrahimi N, Kannan S, Mina L, Herrera-Abreu MT, Òdena A, Sánchez-Guixé M, Capelán M, Azaro A, Bruna A, Rodríguez O, Guzmán M, Grueso J, Viaplana C, Hernández J, Su F, Lin K, Clarke RB, Caldas C, Arribas J, Michiels S, García-Sanz A, Turner NC, Prat A, Nuciforo P, Dienstmann R, Verma CS, Lopez-Bigas N, Scaltriti M, Arnedos M, Saura C, Serra V. High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer. Nat Commun . 2022 Sep 7;13(1):5258. doi: 10.1038/s41467-022-32828-6. Erratum in: Nat Commun . 2022 Nov 14;13(1):6928. PMID: 36071033; PMCID: PMC9452562.
- Duro-Sánchez S, Nadal-Serrano M, Lalinde-Gutiérrez M, Arenas EJ, Bernadó Morales C, Morancho B, Escorihuela M, Pérez-Ramos S, Escrivá-de-Romaní S, Gandullo-Sánchez L, Pandiella A, Esteve-Codina A, Rodilla V, Dijcks FA, Dokter WHA, Cortés J, Saura C, Arribas J. Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody-Drug Conjugates in Breast Cancer. Cancer Res . 2022 Dec 16;82(24):4670-4679. doi: 10.1158/0008-5472.CAN-22-0787. PMID: 36222720; PMCID: PMC9755966.
- Martínez-Sabadell A, Morancho B, Rius Ruiz I, Román Alonso M, Ovejero Romero P, Escorihuela M, Chicote I, Palmer HG, Nonell L, Alemany-Chavarria M, Klein C, Bacac M, Arribas J, Arenas EJ. The target antigen determines the mechanism of acquired resistance to T cell-based therapies. Cell Rep . 2022 Oct 18;41(3):111430. doi: 10.1016/j.celrep.2022.111430. PMID: 36261015.
- Martínez-Sabadell A, Ovejero Romero P, Arribas J, Arenas EJ. Protocol to generate a patient derived xenograft model of acquired resistance to immunotherapy in humanized mice. STAR Protoc . 2022 Oct 26;3(4):101712. doi: 10.1016/j.xpro.2022.101712. PMID: 36317178; PMCID: PMC9617204.
- Martínez-Sabadell A, Arenas EJ, Arribas J. IFNγ Signaling in Natural and Therapy-Induced Antitumor Responses. Clin Cancer Res . 2022 Apr 1;28(7):1243-1249. doi: 10.1158/1078-0432.CCR-21-3226. PMID: 34785585.
- Gámez-Chiachio M, Molina-Crespo Á, Ramos-Nebot C, Martinez-Val J, Martinez L, Gassner K, Llobet FJ, Soriano M, Hernandez A, Cordani M, Bernadó-Morales C, Diaz E, Rojo-Sebastian A, Triviño JC, Sanchez L, Rodríguez-Barrueco R, Arribas J, Llobet-Navás D, Sarrió D, Moreno-Bueno G. Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation. J Exp Clin Cancer Res . 2022 Sep 26;41(1):285. doi: 10.1186/s13046-022-02497-w. PMID: 36163066; PMCID: PMC9511784.
- Bellio C, Emperador M, Castellano P, Gris-Oliver A, Canals F, Sánchez-Pla A, Zamora E, Arribas J, Saura C, Serra V, Tabernero J, Littlefield BA, Villanueva J. GDF15 Is an Eribulin Response Biomarker also Required for Survival of DTP Breast Cancer Cells. Cancers (Basel). 2022 May 23;14(10):2562. doi: 10.3390/cancers14102562. PMID: 35626166; PMCID: PMC9139899.
- Bilal, F., Arenas, E. J., Pedersen, K., Martínez-Sabadell, A., Nabet, B., Guruceaga, E., Vicent, S., Tabernero, J., Macarulla, T. and Arribas, J. The transcription factor Slug uncouples pancreatic cancer progression from the Raf-Mek1/2-Erk1/2 pathway (2021) Cancer Research, accepted
- Arenas, E. J., Martínez-Sabadell, A., Rius Ruiz, I., Román Alonso, M., Escorihuela, M., Luque, A., Fajardo, C. A, Gros, A., Klein, C. Arribas, J. Resistance to HER2-TCB (T cell bispecfic) and -CAR (chimeric antigen receptor) through JAK2 downmodulation (2021). Nature Comm, 12, 1237
- Loo Yau, H., Bell, E., Ettayebi, I., Campos de Almeida, F., Boukhaled, G. M., Shen, S. Y., Allard, D., Morancho, B., Marhon, S. A., Ishak, C. A., Gonzaga, I., Medina, T., Singhania, R., Chakravarthy, A., Chen, R., Mehdipour, P., Pommey, S., Klein, C., Amarante‐Mendes, G., Roulois, D., Arribas, J., Stagg, J. & D. De Carvalho, D. DNA hypomethylating agents increase activation and cytolytic activity of CD8+ T-cells (2020) Molecular Cell, 81, 1469-1483.
- Sanz-Moreno, A., Palomeras, P., Pedersen, K., Morancho, B., Pascual, T., Galván, P., Benítez, S., Gomez-Miragaya, J., Ciscar, M., Jimenez, M., Pernas, S., Petit, A., Soler-Monsó, M. T., Viñas, G., Alsaleem, M., Rakha, E. A., Green, A., R., Santamaria, P. G., Mulder, C., Lemeer, S., Arribas, J., Prat, A., Puig, T., Gonzalez-Suarez, E. RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer (2021) Breast Cancer Res, 23, 42.
- Escorihuela, M., Espinosa-Bravo, M., Peg, V., Dijcks, F. A., Dokter, W. H. A., Cortés, J., Saura, C. & Arribas, J. The Second Generation Antibody-Drug Conjugate SYD985 Overcomes Resistances to T-DM1. Cancers 12, 670–14 (2020).
- Cortés, J., Perez García, J. M., Llombart Cussac, A., Curigliano, G., El Saghir, N. S., Cardoso, F., Barrios, C. H., Wagle, S., Roman, J., Harbeck, N., Eniu, A., Kaufman, P. A., Tabernero, J., García Estévez, L., Schmid, P. & Arribas, J. Enhancing global access to cancer medicines. CA Cancer J Clin 70, 105-124 (2020).
- Serrano, C., Vivancos, A., López-Pousa, A., Matito, J., Mancuso, F. M., Valverde, C., Quiroga, S., Landolfi, S., Castro, S., Dopazo, C., Sebio, A., Virgili, A. C., Menso, M. M., Martín-Broto, J., Sansó, M., García-Valverde, A., Rosell, J., Fletcher, J. A., George, S., Carles, J. & Arribas, J. Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors. BMC Cancer 5;20(1):99 (2020).
- Ferronato, M.J., Nadal Serrano, M., Arenas Lahuerta, E.J., Bernadó Morales, C., Paolillo, G., Martinez-Sabadell Aliguer, A., Santalla, H., Mascaró, M., Vitale, C,. Fall, Y., Arribas, J., Facchinetti, M. M., Curino, A. C. Vitamin D analogues exhibit antineoplastic activity in breast cancer patient-derived xenograft cells. J Steroid Biochem Mol Biol. 105735 (2020). Aug 9;105735. doi: 10.1016/j.jsbmb.2020.105735. Online ahead of print.
- Gris-Oliver, A., Palafox, M., Monserrat, L., Brasó-Maristany, F., Òdena, A., Sánchez-Guixé, M., Ibrahim, Y. H., Villacampa, G., Grueso, J., Parés, M., Guzman, M., Rodríguez, O., Bruna, A., Hirst, C. S., Barnicle, A., de Bruin, E. C., Reddy, A., Schiavon, G., Arribas, J., Mills, G. B., Caldas, C., Dienstmann, R., Prat, A., Nuciforo, P., Razavi, P., Scaltriti, M., Turner, N. C., Saura, C., Davies, B. R., Oliveira, M. & Serra, V. Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts. Clin Cancer Res 26(14):3720-3731 (2020).
- Mateo, L., Duran-Frigola, M., Gris-Oliver, A., Palafox, M., Scaltriti, M., Razavi, P., Chandarlapaty, S., Arribas, J., Bellet, M., Serra, V. & Aloy, P. Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns. Genome Medicine 12, 78–23 (2020).
- García-Valverde, A., Rosell, J., Serna, G., Valverde, C., Carles, J., Nuciforo, P., Fletcher, J. A., Arribas, J., Politz, O. & Serrano, C. Preclinical Activity of PI3K Inhibitor Copanlisib in Gastrointestinal Stromal Tumor. Molecular Cancer Therapeutics 19, 1289–1297 (2020).
- Cebrià-Costa, J. P., Pascual-Reguant, L., Gonzalez-Perez, A., Serra-Bardenys, G., Querol, J., Cosín, M., Verde, G., Cigliano, R. A., 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, T. H. & Peiró, S. LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells. Oncogene 39, 79–121.
- 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, M.P., Fernández-Marcos, P.J., García-Caballero, T., Del Pino, P., Arribas, J., Vidal, A., González-Barcia, M., Serrano, M., Loza, M.I., Domínguez, E., Collado, M. Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat Commun 10(1):4731 (2019)
- 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 Cancer Res 79, 4258-4270 (2019)
- 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. Mol Cancer Ther 18(9):1533-1543 (2019)
- 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 Cancer Letters 453, 34-44 (2019)
- 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 Scientific Reports 9, 3352 (2019)
- Blasco-Benito, S., Moreno, E., Seijo-Vila, M., Tundidor, I., Andradas, C., Caffarel, M.M., Caro-Villalobos, M., Urigüen, L., Diez-Alarcia, R., Moreno-Bueno, G., Hernández, L., Manso, L., Homar-Ruano, P., McCormick, P.J., Bibic, L., Bernadó Morales, C., Arribas, J., Canals, M., Casadó, V., Canela, E.I., 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. 116(9) 3863-3872 (2019)
- Kang, S.A., Guan, J.S., Tan, H.J., Chu, T., Thike, A.A., Bernadó Morales, C., Arribas, J., Wong, C.Y., Tan, P.H., Gudi, M., Putti, T.C., Sohn, J., Lim, S.H., Lee, S.C,. Lim, Y.P. 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 25(8):2588-2600 (2019)
- Lambies, G., Miceli, M., Martínez-Guillamon, C., Olivera-Salguero, R., Peña, R., Frías, C.P., Calderón, I., Atanassov, B.S., Dent, S.Y.R., Arribas, J., García de Herreros, A., Díaz, V.M. TGFβ-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1. Cancer Res 79(1):33-46 (2019)
- 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. Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib. The Oncologist. 24(5):680-687 (2019)
- Rius Ruiz I*, Vicario R*, Morancho B, Bernadó Morales C, Arenas EJ, Herter S, Freimoser-Grundschober A, Somandin J, Sam J, Ast O, Martínez Barriocanal Á, Luque A, Escorihuela M, Varela I, Cuartas I, Nuciforo P, Fasani R, Peg V, Rubio I, Cortés J, Serra V, Escriva-de-Romani S, Sperinde J, Chenna A, Huang W, Winslow J, Albanell J, Seoane J, Scaltriti M, Baselga J, Tabernero J, Umana P, Bacac M, Saura C†, Klein C†, Arribas J†, ‡. p95HER2-T cell bispecific antibody for breast cancer treatment. Sci Transl Med 10(461) pii: eaat1445 (2018)
- Cruz C, Llop-Guevara A, Garber JE, Arun BK, Pérez Fidalgo JA, Lluch A, Telli ML, Fernández C, Kahatt C, Galmarini CM, Soto-Matos A, Alfaro V, Pérez de la Haza A, Domchek SM, Antolin S, Vahdat L, Tung NM, Lopez R, Arribas J, Vivancos A, Baselga J, Serra V, Balmaña J, Isakoff SJ. Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy. J Clin Oncol 36, 3134-3143 (2018)
- Mendez O, Peg V, Salvans C, Pujals M, Fernandez Y, Abasolo I, Perez J, Matres A, Valeri M, Gregori J, Villarreal L, Schwartz S, Ramon Y Cajal S, Tabernero J, Cortes J, Arribas J, Villanueva J. Extracellular HMGA1 promotes tumor Invasion and Metastasis in Triple-Negative Breast Cancer. Clin Cancer Res 24(24):6367-6382 (2018)
- Georgilis A, Klotz S, Hanley CJ, Herranz N, Weirich B, Morancho B, Leote AC, D’Artista L, Gallage S, Seehawer M, Carroll T, Dharmalingam G, Wee KB, Mellone M, Pombo J, Heide D, Guccione E, Arribas J, Barbosa-Morais NL, Heikenwalder M, Thomas GJ, Zender L, Gil J. PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells. Cancer Cell 34(1):85-102.e9 (2018)
- 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, Martin M. Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth. Mol Oncol 12(8):1383-1397 (2018)
- Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, Llop-Guevara A, Ibrahim YH, Gris-Oliver A, Bonache S, Morancho B, Bruna A, Rueda OM, Lai Z, Polanska UM, Jones GN, Kristel P, de Bustos L, Guzman M, Rodríguez O, Grueso J, Montalban G, Caratú G, Mancuso F, Fasani R, Jiménez J, Howat WJ, Dougherty B, Vivancos A, Nuciforo P, Serres-Créixams X, Rubio IT, Oaknin A, Cadogan E, Barrett JC, Caldas C, Baselga J, Saura C, Cortés J, Arribas J, Jonkers J, Díez O, O’Connor MJ, Balmaña J, Serra V. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol 29(5):1203-1210 (2018)
- 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 20, 211-221 (2018)
- Floros KV, Lochmann TL, Hu B, Monterrubio C, Hughes MT, Wells JD, Bernadó Morales C, Ghotra MS, Costa C, Souers AJ, Boikos SA, Leverson JD, Tan M, Serra V, Koblinski JE, Arribas J, Prat A, Paré L, Miller TW, Dozmorov MG, Harada H, Windle BE, Scaltriti M, Faber AC. Co-amplification of miR-4728 protects HER2-amplified breast cancers from targeted therapy. Proc Natl Acad Sci U S A 115(11):E2594-E2603 (2018)
- 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. Oncotarget 8(55):93688-93703 (2017)
- Ríos-Luci, C., García-Alonso S., Díaz-Rodríguez E., Nadal-Serrano, M., Arribas, J., Ocaña, A. and Pandiella, A. Resistance to the Antibody-Drug Conjugate T-DM1 Is Based in a Reduction in Lysosomal Proteolytic Activity. Cancer Res 77(17):4639-4651 (2017)
- 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 23(22):7006-7019 (2017)
- 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 36(40):5639-5647 (2017)
- 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. Interrogating open issues in cancer precision medicine with Patient-Derived Xenografts. Nature Rev Cancer 17, 254-268 (2017)
- Morancho, B., Zacarías-Fluck, M., Esgueva, A., Bernadó Morales, C. Di Cosimo, S., Prat, A., Cortés, J., Arribas, J.* and Rubio, I. T.* Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts. Oncotarget 7(42) :67956-67965 (2016)
- Hutchinson, E., Pujana M. A. and Arribas, J. Cancer therapeutic resistance: progress and perspectives. Drugs of Today 52 – 6, 347-354 (2016)
- 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 8(1):88 (2016)
- 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. 7(35):56295-56308 (2016)
- Esparís-Ogando, A., Montero, J. C., Arribas, J., Ocaña, A. and Pandiella, A. Targeting the EGF/HER Ligand-Receptor System in Cancer. Curr Pharm Des 22(39):5887-5898 (2016)
- 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. Molecular Oncology 10(1):138-47 (2016)
- Morancho, B.*, Martínez-Barriocanal, A.*, Villanueva, J. and Arribas, J‡. Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence. Breast Cancer Res 17, 106 (2015)
- Vicario R, Peg V, Morancho B, Zacarias-Fluck M, Zhang, J., Martinez-Barriocanal A, Navarro Jiménez A, Aura C, Burgues O, Lluch A, Cortés 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 10(6):e0129876 (2015)
- Massó-Vallés, D., Jauset, T., Serrano, E., Pedersen, K., Affara, N., Whitfield, J., Beaulieu, M. -E., Sodir, N., Evan, G. I., Elias, L., Arribas, J. and Soucek, L. Ibrutinib exerts potent antifibrotic and antitumor activities in mouse models of pancreatic adenocarcinoma. Cancer Res 75, 1675-1681 (2015)
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- Comment on this article in J Natl Cancer Inst 107(5): djv091 (2015)
- Scaltriti, M., Nuciforo, P., Bradbury. I, Sperinde, J., Agbor-Tarh, D., Chenna, A., Winslow, J., Serra, V., Parra, J.-Ll. 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 21, 569-576 (2015)
- Immune Senolysis Against Breast Cancer. Breast Cancer Research Foundation. PI: Joaquín Arribas. 2024 – 2025
- Redirection of T cells against HER2-driven tumors.
Asociación Española Contra el Cáncer (AECC). Grupos Coordinados AECC 2019.
Coordinator: Joaquín Arribas.
2019-2024. - Immunotherapy against HER2 positive tumors. PI19/01181.
Instituto Salud Carlos III (ISCIII).
PI: Joaquín Arribas.
2020-2022. - Conjugados Anticuerpo-Droga contra HER2: Mecanismos de Resistencia y Combinaciones Terapéuticas.
Fundación Mutua Madrileña.
Co-PIs: Joaquín Arribas, Javier Cortés.
2018-2021. - Horizon 2020 call SC1-PM-02-2017. Consortium 14 Partners.
Coordinator: Annette Byrne.
PI: Joaquín Arribas.
2018-2023. - EDIReX: EurOPDX Distributed Infrastructure for Research on patient-derived cancer Xenografts. 731105.
Horizon 2020 call H2020-INFRAIA 2016-2017.
Consortium 19 Partners.
Coordinator: Enzo Medico.
PI: Joaquín Arribas.
2018-2022. - Preclinical development of anti-PD-L2 immunomodulatory antibodies for the treatment of pathologies induced by cell damage-Validation of the strategy in residual tumors and fibrosis (IMMOPDL2)
Role: Co-applicant como entidad OPI. I+D+I en el proyecto de la convocatoria 2017 RETOS-COLABORACIÓN, bajo la referencia externa de proyecto: RTC2017-6123-1.
2018-2020.
PI: Joaquin Arribas
Proyecto financiado por el Ministerio de Ciencia e Innovación
El presente proyecto está cofinanciado por el Fondo Europeo de Desarrollo Regional. Objetivo Temático: Promover el desarrollo tecnológico, la innovación y una investigación de calidad.
7. Immune-Image. Horizon 2020 call IMI2-2018-14-02. Consortium of 22 partners.
Financing entity: European Commission – Horizon 2020
Coordinator: Albert D Windhorst
PI Joaquín Arribas
Duration: 01/10/2019 – 30/09/2024
8. Comprehensive Program of Cancer Immunotherapy & Immunology II (CAIMI-II)
Financing entity: Fundación BBVA
Coordinator: Josep Tabernero
PI: Joaquín Arribas
Duration: 01/01/2022 – 31/12/2025
9. Immune Senolysis Against Breast Cancer
Financing entity: Breast Cancer Research Foundation (BCRF)
PI: Joaquín Arribas
Duration: 1/10/2022-30/09/2023
10. Horizon 2020 call H2020-INFRAIA 2016-2017. Consortium 19 Partners.
Financing entity: European Commission – Horizon 2020
Coordinator: Enzo Medico.
PI: Joaquín Arribas.
Duration: 1/02/2018-31/07/2022
11. Immune Senolysis Against Breast Cancer
Financing entity: Breast Cancer Research Foundation
PI: Joaquín Arribas.
Duration: 01/10/2023 – 30/09/2024