19th Ave New York, NY 95822, USA

Grupo de Terapéutica Experimental

Experimental Therapeutics Group

Nuestro grupo lleva a cabo investigaciones preclínicas del cáncer de mama para avanzar en el conocimiento de los biomarcadores de respuesta a las terapias dirigidas. Para ello, generamos modelos preclínicos como los xenoinjertos derivados del paciente (PDX) y los cultivos derivados del paciente (PDC) a partir de muestras de pacientes con cáncer de mama.

Hemos contribuido significativamente al campo de la resistencia a los inhibidores de PI3K y seguimos ahondando en los mecanismos de resistencia a los inhibidores de CDK4/6, los inhibidores de FGFR, los inhibidores de AKT y los moduladores de AR (SARM) en los tumores de mama.

Animados por el éxito temprano de los inhibidores de reparación del daño del ADN en tumores mutados BRCA1/2 de la línea germinal, iniciamos un proyecto destinado a identificar los biomarcadores de respuesta de los inhibidores de PARP (iPARP), así como otros inhibidores de reparación del daño del ADN, incluidos los dirigidos a WEE1 o ATR. Nuestros estudios respaldan la capacidad de los tumores mutantes BRCA de la línea germinal para recuperar la funcionalidad HRR y desarrollar resistencia a iPARP.

Hemos desarrollado un ensayo, la prueba RAD51predict, que identifica con precisión los tumores BRCA de la línea germinal que han recuperado la funcionalidad HRR y se vuelven resistentes a estos fármacos. Es importante destacar que esta prueba también identifica los tumores sensibles a iPARP por las alteraciones de HRR más allá de la condición de BRCA de la línea germinal. Presentamos una patente (solicitud para la UE en 2017 y PCT en 2018) y actualmente estamos validando el uso de esta prueba en muestras tumorales de pacientes con cáncer de mama, ovario y próstata.

En resumen, nuestro equipo ha avanzado significativamente en la comprensión del modo de acción de las nuevas terapias dirigidas, ha identificado nuevos biomarcadores de respuesta y ha desarrollado un ensayo basado en biomarcadores con potencial aplicación clínica. También hemos demostrado la eficacia de las combinaciones de fármacos basadas en hipótesis.

Violeta Serra
Jefa de grupo
  • Desarrollo de biomarcadores predictivos de tratamientos dirigidos en cánceres de mama ER+ y triple negativo, incluidos los inhibidores dirigidos contra la proteína PARP de reparación del daño del ADN y contra las quinasas de señalización / ciclo celular (CDK4/6, PI3K/AKT o FGFR).
  • Explorar nuevas combinaciones de tratamientos para los cánceres de mama ER+ y triple negativo.
  • Contribución a la medicina personalizada mediante el desarrollo de una prueba diagnóstica para orientar mejor las estrategias de tratamiento basadas en inhibidores de PARP.
  • Establecimiento de modelos preclínicos de cáncer de mama derivados de tumores de pacientes para explorar terapias combinatorias basadas en hipótesis.

Figure: RAD51predict (predictor of PARPi response) is an immunofluorescence assay, performed on FFPE tumor sections, that identifies nuclear biomarkers and determines the functionality of the HRR DNA-damage pathway and the response to PARPi therapy. It has been validated in PDX models and we are currently extending the clinical validation to several tumor types.

Experimental Therapeutics Group
Jefa de grupo
Violeta Serra
Becarios postdoctorales
Alba Llop-Guevara
Marta Palafox
Mónica Sánchez
Estudiantes de postgrado
Laia Monserrat
Flaminia Pedretti
Andrea Herencia
Estudiantes visitantes
Andreu Òdena
Cristina Molina
Técnicas
Judit Grueso
Olga Rodríguez

Publicaciones científicas más relevantes

  • Pellegrino B, Mateo J, Serra V, Balmaña J. Controversies in oncology: are genomic tests quantifying homologous recombination repair deficiency (HRD) useful for treatment decision making? ESMO Open. 2019 May 9;4(2):e000480.
  • Mateo J, Lord CJ, Serra V, Tutt A, Balmaña J, Castroviejo-Bermejo M, Cruz C, Oaknin A, Kaye SB, de Bono JS. A decade of clinical development of PARP inhibitors in perspective. Ann. Oncol. 2019 Sep 1;30(9):1437-1447.
  • Gourley C, Balmaña J, Ledermann JA, Serra V, Dent R, Loibl S, Pujade-Lauraine E, Boulton SJ. Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy. J. Clin. Oncol. 2019 Sep 1;37(25):2257-2269.
  • Green JL, Okerberg ES, Sejd J, Palafox M, Monserrat L, Alemayehu S, Wu J, Sykes M, Aban A, Serra V, Nomanbhoy T. Direct CDKN2 Modulation of CDK4 Alters Target Engagement of CDK4 Inhibitor Drugs. Mol. Cancer Ther. 2019 Apr;18(4):771-779.
  • 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, and Serra V. RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol. 2018 May 1;29(5):1203-1210.
  • Castroviejo-Bermejo M, Cruz C, Llop-Guevara A, Gutiérrez-Enríquez S, Ducy M, Ibrahim YH, Gris-Oliver A, Pellegrino B, Bruna A, Guzmán M, Rodríguez O, Grueso J, Bonache S, Moles-Fernández A, Villacampa G, Viaplana C, Gómez P, Vidal M, Peg V, Serres-Créixams X, Dellaire G, Simard J, Nuciforo P, Rubio IT, Dientsmann R, Barrett JC, Caldas C, Baselga J, Saura C, Cortés J, Déas O, Jonkers J, Masson JY, Cairo S, Judde JG, O’Connor MJ, Díez O, Balmaña J, and Serra V. A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation. EMBO Mol Med. 2018 Dec;10(12).
  • 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, and Isakoff SJ. Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy. J Clin Oncol. 2018 Nov 1;36(31):3134-3143.
  • 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 Feb;20(2):211-221.
  • Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, Belen García A, Martínez-Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA. Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun. 2017 Nov 2;8(1):1278.
  • Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, (…), Serra V, (…), Carracedo A. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature. 2017 Jul 6;547(7661):109-113.
  • Hierro C, Alsina M, Sánchez M, Serra V, Rodon J, Tabernero J. Targeting the fibroblast growth factor receptor 2 in gastric cancer: promise or pitfall? Ann Oncol. 2017 Jun 1;28(6):1207-1216.
  • 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 Interrogating open issues in cancer precision medicine with Patient-Derived Xenografts. Nat Rev Cancer. 2017 Apr; 17(4):254-268.
  • Bruna A, Rueda OM, Greenwood W, Batra AS, Callari M, Batra RN, Pogrebniak K, Sandoval J, Cassidy JW, Tufegdzic-Vidakovic A, Sammut SJ, Jones L, Provenzano E, Baird R, Eirew P, Hadfield J, Eldridge M, McLaren-Douglas A, Barthorpe A, Lightfoot H, O’Connor MJ, Gray J, Cortes J, Baselga J, Marangoni E, Welm AL, Aparicio S, Serra V, Garnett MJ, Caldas C. A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds. Cell. 2016 Sep 22;167(1):260-274.e22.
  • Brasó-Maristany F, Filosto S, Catchpole S, Marlow R, Quist J, Francesch-Domenech E, Plumb DA, Zakka L, Gazinska P, Liccardi G, Meier P, Gris-Oliver A, Cheang MCU, Perdrix-Rosell A, Shafat M, Noël E, Patel N, McEachern K, Scaltriti M, Castel P, Noor F, Buus R, Mathew S, Watkins J, Serra V, Marra P, Grigoriadis A & Tutt AN. PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nat Med. 2016 Nov;22(11):1303-1313.
  • Drost R, Dhillon KK, van der Gulden H, van der Heijden I, Brandsma I, Cruz C, Chondronasiou D, Castroviejo-Bermejo M, Boon U, Schut E, van der Burg E, Wientjens E, Pieterse M, Klijn C, Klarenbeek S, Loayza-Puch F, Elkon R, van Deemter L, Rottenberg S, van de Ven M, Dekkers DH, Demmers JA, van Gent DC, Agami R, Balmaña J, Serra V, Taniguchi T, Bouwman P, Jonkers J. BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1. J Clin Invest. 2016 Aug 1;126(8):2903-18.
  • Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor positive breast cancer.Herrera-Abreu M*, Palafox M*, Asghar U, Rivas MA, Cutts RJ, Garcia-Murillas I, Pearson A, Guzman M, Rodriguez O, Grueso J, Bellet M, Cortés J, Elliott R, Pancholi S, Baselga J, Dowsett M, Martin LA, Turner NC*, Serra V*. Cancer Research. 2016 Apr 1;76(8):2301-13. IF: 9.329
  • The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapy Resistance. Wang Y, Bernhardy AB, Cruz C, Krais JJ, Nacson J, Nicolas E, Peri S, van der Gulden H, van der Heiiden I, O’Brien SW, Zhang Y, Harrell MI, Johnson SF, Candido Dos Reis FJ, Pharoah PDP, Karlan B, Gourley C, Lambrechts D, Chenevix-Trench G, Olsson H, Benitez JJ, Greene MH, Gore M, Nussbaum R, Sadetzki S, Gayther SA, Kjaer SK, kConFab Investigators, D’Andrea AD, Shapiro GI, Wiest DL, Connolly DC, Daly MB, Swisher EM, Bouwman P, Jonkers J, Balmaña J, Serra V and Johnson N. Cancer Research. 2016, May 1;76(9):2778-90. IF: 9.329/ D=1. Citations#=0
  • MEK plus PI3K/mTORC1/2 therapeutic efficacy is impacted by TP53 mutation in preclinical models of colorectal cancer. García-García C, Rivas MA, Ibrahim YH, Calvo MT, Gris-Oliver A, Rodriguez O, Grueso J, Anton P, Guzman M, Aura C, Nuciforo P, Jessen K, Argiles G, Dienstmann R, Bertotti A, Trusolino L, Matito J, Vivancos A, Chicote I, Palmer HG, Tabernero J, Scaltriti M, Baselga J*, Serra V*. Clin Cancer Res. 2015 Dec 15;21(24):5499-510. IF: 8.722/ D=1. Citations#=1
  • PI3K inhibition results in enhanced estrogen receptor function and dependence in  hormone receptor-positive breast cancer. Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y, Cortes J, Perez-Garcia J, Galvan P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen N, Chandarlapaty S, Scaltriti M, Baselga J. Sci Transl Med. 2015 Apr 15;7(283):283ra51. IF: 14.414 / D=1. Citations#=26
  • Targeting a cell state common to triple-negative breast cancers. Muellner MK, Mair B, Ibrahim Y, Kerzendorfer C, Lechtermann H, Trefzer C, Klepsch F, Müller AC, Leitner E, Macho-Maschler S, Superti-Furga G, Bennett KL, Baselga J, Rix U, Kubicek S, Colinge J, Serra V, Nijman SM. Mol Syst Biol. 2015 Feb 19;11:789. IF: 14.099 / D=1. Citations#=4
  • High HER2 expression correlates with response to the combination of lapatinib and trastuzumab. 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 CE, Eidtmann H, Arribas J, Cortes J, De Azambuja E, Piccart M, Baselga J. Clin Cancer Res. 2014 Dec 2. pii:clincanres.1824. IF: 8.193 / D=1. Citations#=17
  • Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy. Parra-Palau JL, Morancho B, PegV, 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. JNCI, 2014: 106(11) pii: dju291. IF: 15.161 / D=1. Citations#=12
  • Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Dienstmann R, Rodon J, Serra V, Tabernero J. Mol Cancer Ther. 2014: 13(5), 1021-31. IF: 6.107 / Q=1. Citations#=82
  • Evaluation and Clinical Analyses of Downstream Targets of the Akt Inhibitor GDC-0068. *Serra V, *Yan Y, Prudkin L, Scaltriti M, Murli S, Rodríguez O, Guzman M, Sampath D, Nannini M, Xiao Y, Wagle MC, Wu JQ, Wongchenko M, Hampton G, Ramakrishnan V, Lackner MR, Saura C, Roda D, Cervantes A, Tabernero J, Patel P, Baselga J. Clin Cancer Res. 2013: 19(24), 6976-86. IF: 8.193 / D=1. Citations#=19
  • Clinical response to lapatinib therapy of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation. 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 PG, Scaltriti M, Seoane J, Baselga J. Cancer Discovery. 2013: 3(11), 1238-44. IF: 15.929 / D=1. Citations#=10
  • mTORC1 inhibition is required for sensitivity to PI3K p110-α inhibitors in PIK3CA-mutant breast cancer. Elkabets M, Vora S, Juric D, Morse N, Mino-Kenudson N, Muranen T, Tao J, Bosch Campos A, Rodon J, Ibrahim YH, Serra V, Rodrik-Outmezguine V, Quadt C, Huang A, Brugge J, Rosen N, Engelman JA, Scaltriti M, Baselga J. Science Translational Medicine. 2013: 5(196): 196ra99. IF: 14.414 / D=1. Citations#=80
  • RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. *Serra V, *Eichhorn PJA, García-García C, Ibrahim YH, Prudkin L, Sánchez G, Rodríguez O, Antón P, Parra JLL, Marlow S, Scaltriti M, Pérez-Garcia J, Prat A, Arribas J, Hahn WC, Kim SY, Baselga J. J Clin Invest. 2013: 123(6), 2551-63. IF: 13.765 / D=1. Citations#=35
  • Development of PI3K inhibitors: lessons learned from early clinical trials. Rodon J, Dienstmann R, Serra V, Tabernero J. Nat Rev Clin Oncol. 2013: 10(3), 143-53. IF: 15.696 / D=1. Citations#=289
  • PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA proficiente triple negative breast cancer to PARP inhibition. Ibrahim Y H, García-García C, Serra V, He L, Torres-Lockhart K, Prat A, Anton P, Cózar P, Guzmán M, Grueso J, Rodríguez O, Calvo M T, Aura C, Diez O, Rubio I, Pérez J, Rodón J, Cortés J, Ellisen LW, Scaltriti M, Baselga J. Cancer Discovery. 2012: 2(11), 1036-47. IF: 15.929 / D=1. Citations#=167
  • Dual mTORC1/2 and HER2 Blockade Results in Antitumor Activity in Preclinical Models of Breast Cancer Resistant to Anti-HER2 Therapy. *García-García C, *Ibrahim YH, Serra V, Calvo MT, Guzmán M, Grueso J, Aura C, Pérez J, Jessen K, Liu Y, Rommel C, Tabernero J, Baselga J, Scaltriti M. Clin Cancer Res. 2012: 1:18(9), 2603-12. IF: 8.193 / D=1. Citations#=86
  • Anti-tumor activity of IPI-504, an Hsp90 inhibitor, in HER2 positive trastuzumab-resistant breast cancer. *Serra V, *Scaltriti M, Normant E, Guzman M, Rodriguez O, Lim AR, Slocum KL, West KA, Rodriguez V, Prudkin L, Jimenez J, Aura C and Baselga J. Molecular Cancer Ther. 2011: 10(5), 817-24. IF: 6.107 / Q=1. Citations#=33
  • Cyclin E amplification/overexpression, a novel mechanism of trastuzumab resistance in HER2 positive breast cancer patients. *Scaltriti M, *Eichhorn P, Cortés J, Prudkin L, Aura CM, Jiménez J, Chandarlapaty S, Serra V, Prat A, Ibrahim YH, Guzmán M, Gili M, Rodríguez O, Rodríguez S, Pérez J, Green SR, Mai S, Rosen N, Hudis C and Baselga J. PNAS. 2011: 108(9), 3761-6. IF: 9.809 / D=1. Citations#=140
  • PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2 overexpressing breast cancer. Serra V, Scaltriti M, Prudkin L, Eichhorn P, Ibrahim YH, Chandarlapaty S, Markman B, Rodriguez O, Guzman M, Rodriguez S, Gili M, Russillo M, Parra JL, Singh S, Arribas J, Rosen N, and Baselga J. Oncogene. 2011: 30(22), 2547-57. IF: 8.559 / D=1. Citations#=275
  • AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N. Cancer Cell. 2011: 19(1), 58-71. IF: 23.893 / D=1. Citations#=511
  • Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, Baselga J. Cancer Research. 2008: 68(22), 9221-30. IF: 9.284 / D=1. Citations#=375
  • NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, Botero ML, Llonch E, Atzori F, Di Cosimo S, Maira M, Garcia-Echeverria C, Parra JL, Arribas J, Baselga J. Cancer Research. 2008: 68(19), 8022-30. IF: 9.284 / D=1. Citations#=589

Todas las publicaciones

  • Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, Belen García A, Martínez-Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA. Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun. 2017 Nov 2;8(1):1278.
  • Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, (…), Serra V, (…), Carracedo A. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature. 2017 Jul 6;547(7661):109-113.
  • Hierro C, Alsina M, Sánchez M, Serra V, Rodon J, Tabernero J. Targeting the fibroblast growth factor receptor 2 in gastric cancer: promise or pitfall? Ann Oncol. 2017 Jun 1;28(6):1207-1216.
  • 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 Interrogating open issues in cancer precision medicine with Patient-Derived Xenografts. Nat Rev Cancer. 2017 Apr; 17(4):254-268.
  • CDK12 inhibition reverses de novo and acquired PARP inhibitor resistance in BRCA wild-type and mutated models of triple-negative breast cancer. Johnson SF, Cruz C, Greifenberg AK, Dust S, Stover DG, Chi D, Primack B, Cao S, Bernhardy AJ, Coulson R, Lazaro JB, Kachupurakkal B, Sun H, Unitt C, Moreau LA, Sarosiek KA, Scaltriti M, Juric D, Baselga J, Richardson AL, Rodig SJ, D’Andrea AD, Balmaña J, Johnson N, Geyer M, Serra V, Lim E, Shapiro GI. Cell Reports. Nov 22;17(9):2367-2381. doi: 10.1016/j.celrep.2016.10.077. IF: 7.870
  • PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Brasó-Maristany F, Filosto S, Catchpole S, Marlow R, Quist J, Francesch-Domenech E, Plumb DA, Zakka L, Gazinska P, Liccardi G, Meier P, Gris-Oliver A, Cheang MCU, Perdrix-Rosell A, Shafat M, Noël E, Patel N, McEachern K, Scaltriti M, Castel P, Noor F, Buus R, Mathew S, Watkins J, Serra V, Marra P, Grigoriadis A & Tutt AN. Nat Med. Nov;22(11):1303-1313. IF: 30.357.
  • A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds. Bruna A, Rueda OM, Greenwood W, Batra AS, Callari M, Batra RN, Pogrebniak K, Sandoval J, Cassidy JW, Tufegdzic-Vidakovic A, Sammut SJ, Jones L, Provenzano E, Baird R, Eirew P, Hadfield J, Eldridge M, McLaren-Douglas A, Barthorpe A, Lightfoot H, O’Connor MJ, Gray J, Cortes J, Baselga J, Marangoni E, Welm AL, Aparicio S, Serra V, Garnett MJ, Caldas C. Cell. 2016 Sep 22;167(1):260-274.e22. IF: 28.710.
  • Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity. Mair B, Konopka T, Kerzendorfer C, Sleiman K, Salic S, Serra V, Muellner MK, Theodorou V, Nijman SM. PLoS Genet. 2016 Sep 2;12(9):e1006279. IF: 7.528.
  • Stratification and therapeutic potential of PML in metastatic breast cancer. Martín-Martín N, Piva M, Urosevic J, Aldaz P, Sutherland JD, Fernández-Ruiz S, Arreal L, Torrano V, Cortazar AR, Planet E, Guiu M, Radosevic-Robin N, Garcia S, Macías I, Salvador F, Domenici G, Rueda OM, Zabala-Letona A, Arruabarrena-Aristorena A, Zúñiga-García P, Caro-Maldonado A, Valcárcel-Jiménez L, Sánchez-Mosquera P, Varela-Rey M, Martínez-Chantar ML, Anguita J, Ibrahim YH, Scaltriti M, Lawrie CH, Aransay AM, Iovanna JL, Baselga J, Caldas C, Barrio R, Serra V, Vivanco Md, Matheu A, Gomis RR, Carracedo A. Nat Commun. 2016 Aug 24;7:12595. IF: 11.329.
  • Cancer network activity associated with therapeutic response and synergism. 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. Genome Med. 2016 Aug 24;8(1):88. IF: 5.850.
  • BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1. Drost R, Dhillon KK, van der Gulden H, van der Heijden I, Brandsma I, Cruz C, Chondronasiou D, Castroviejo-Bermejo M, Boon U, Schut E, van der Burg E, Wientjens E, Pieterse M, Klijn C, Klarenbeek S, Loayza-Puch F, Elkon R, van Deemter L, Rottenberg S, van de Ven M, Dekkers DH, Demmers JA, van Gent DC, Agami R, Balmaña J, Serra V, Taniguchi T, Bouwman P, Jonkers J. J Clin Invest. 2016 Jul 25. pii: 70196. IF: 12.575.
  • Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor positive breast cancer. Herrera-Abreu M, Palafox M, Asghar U, Rivas MA, Cutts RJ, Garcia-Murillas I, Pearson A, Guzman M, Rodriguez O, Grueso J, Bellet M, Cortés J, Elliott R, Pancholi S, Baselga J, Dowsett M, Martin LA, Turner NC, Serra V*. Cancer Res. 2016 Apr 1;76(8):2301-13. IF: 9.329.
  • The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapy Resistance. Wang Y, Bernhardy AB, Cruz C, Krais JJ, Nacson J, Nicolas E, Peri S, van der Gulden H, van der Heiiden I, O’Brien SW, Zhang Y, Harrell MI, Johnson SF, Candido Dos Reis FJ, Pharoah PDP, Karlan B, Gourley C, Lambrechts D, Chenevix-Trench G, Olsson H, Benitez JJ, Greene MH, Gore M, Nussbaum R, Sadetzki S, Gayther SA, Kjaer SK, kConFab Investigators, D’Andrea AD, Shapiro GI, Wiest DL, Connolly DC, Daly MB, Swisher EM, Bouwman P, Jonkers J, Balmaña J, Serra V and Johnson N. Cancer Res. 2016, May 1;76(9):2778-90. IF: 9.329.
  • 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
  • Ugalde-Olano A, Egia A, Fernández-Ruiz S, Loizaga-Iriarte A, Zuñiga-García P, Garcia S, Royo F, Lacasa-Viscasillas I, Castro E, Cortazar AR, Zabala-Letona A, Martín-Martín N, Arruabarrena-Aristorena A, Torrano-Moya V, Valcárcel-Jiménez L, Sánchez-Mosquera P, Caro-Maldonado A, González-Tampan J, Cachi-Fuentes G, Bilbao E, Montero R, Fernández S, Arrieta E, Zorroza K, Castillo-Martín M, Serra V, Salazar E, Macías-Cámara N, Tabernero J, Baselga J, Cordon-Cardo C, Aransay AM, Villar AD, Iovanna JL, Falcón-Pérez JM, Unda M, Bilbao R, Carracedo A.  Methodological aspects of the molecular and histological study of prostate cancer: focus on PTEN. Methods 2015 May; 77-78: 25-30
  • García-García C, Rivas MA, Ibrahim YH, Calvo MT, Gris-Oliver A, Rodriguez O, Grueso J, Anton P, Guzman M, Aura C, Nuciforo P, Jessen K, Argiles G, Dienstmann R, Bertotti A, Trusolino L, Matito J, Vivancos A, Chicote I, Pálmer HG, Tabernero J, Scaltriti M, Baselga J, Serra V.  MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer. Clin. Cancer Res. 2015 Dec; 21(24): 5499-510
  • Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y, Cortes J, Pérez-García J, Galván P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen N, Chandarlapaty S, Scaltriti M, Baselga J.  PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med 2015 Apr; 7(283): 283ra51
  • Muellner MK, Mair B, Ibrahim Y, Kerzendorfer C, Lechtermann H, Trefzer C, Klepsch F, Müller AC, Leitner E, Macho-Maschler S, Superti-Furga G, Bennett KL, Baselga J, Rix U, Kubicek S, Colinge J, Serra V, Nijman SM.  Targeting a cell state common to triple-negative breast cancers. Mol. Syst. Biol. 2015 Jan; 11(1): 789
  • 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)
  • Dienstmann R, Rodón J, Serra V, Tabernero J.  Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol. Cancer Ther. 2014 May; 13(5): 1021-31
  • Rodón J, Dienstmann R, Serra V, Tabernero J.  Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol 2013 Mar; 10(3): 143-53
    Yan Y, Serra V, Prudkin L, Scaltriti M, Murli S, Rodriguez O, Guzman M, Sampath D, Nannini M, Xiao Y, Wagle MC, Wu JQ, Wongchenko M, Hampton G, Ramakrishnan V, Lackner MR, Saura C, Roda D, Cervantes A, Tabernero J, Patel P, Baselga J.  Evaluation and clinical analyses of downstream targets of the Akt inhibitor GDC-0068. Clin. Cancer Res. 2013 Dec; 19(24): 6976-86
  • 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
  • Elkabets M, Vora S, Juric D, Morse N, Mino-Kenudson M, Muranen T, Tao J, Campos AB, Rodón J, Ibrahim YH, Serra V, Rodrik-Outmezguine V, Hazra S, Singh S, Kim P, Quadt C, Liu M, Huang A, Rosen N, Engelman JA, Scaltriti M, Baselga J.  mTORC1 inhibition is required for sensitivity to PI3K p110α inhibitors in PIK3CA-mutant breast cancer. Sci Transl Med 2013 Jul; 5(196): 196ra99
  • Ibrahim YH, García-García C, Serra V, He L, Torres-Lockhart K, Prat A, Anton P, Cozar P, Guzman M, Grueso J, Rodriguez O, Calvo MT, Aura C, Diez O, Rubio IT, Pérez J, Rodón J, Cortes J, Ellisen LW, Scaltriti M, Baselga J.  PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition. Cancer Discov 2012 Nov; 2(11): 1036-47
  • García-García C, Ibrahim YH, Serra V, Calvo MT, Guzman M, Grueso J, Aura C, Pérez J, Jessen K, Liu Y, Rommel C, Tabernero J, Baselga J, Scaltriti M.  Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy. Clin. Cancer Res. 2012 May; 18(9): 2603-12
  • 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
  • Scaltriti M, Eichhorn PJ, Cortes J, Prudkin L, Aura C, Jimenez J, Chandarlapaty S, Serra V, Prat A, Ibrahim YH, Guzman M, Gili M, Rodriguez O, Rodriguez S, Pérez J, Green SR, Mai S, Rosen N, Hudis C, Baselga J.  Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc. Natl. Acad. Sci. U.S.A. 2011 Mar; 108(9): 3761-6
  • Scaltriti M, Serra V, Normant E, Guzman M, Rodriguez O, Lim AR, Slocum KL, West KA, Rodriguez V, Prudkin L, Jimenez J, Aura C, Baselga J.  Antitumor activity of the Hsp90 inhibitor IPI-504 in HER2-positive trastuzumab-resistant breast cancer. Mol. Cancer Ther. 2011 May; 10(5): 817-24
  • Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N.  AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011 Jan; 19(1): 58-71
  1. Project Title: “Development of new therapeutic strategies to overcome resistance to CDK4/6 inhibitors in breast cancers with expression of the estrogen receptor” (PI20/00892)
    Principal Investigators: Violeta Serra & M. Bellet
    Funding Agency: ISCIII-Project Grant
    Duration: 2021-2023
  2. Project Title: “PARPiPRED, diagnostic test that facilitates personalized medicine in cancer treatment” (2019PROD00045)
    Principal Investigator: Violeta Serra
    Funding Agency: AGAUR-Producte
    Duration: 2020-2021
  3. Project Title: “RAD51predict: Patient stratification based on DNA repair functionality for cancer precision medicine” (ERAPERMED2019-215)
    Coordinator: Violeta Serra
    Funding Agency: ERA Net- Era PerMed
    Partner Institutions: University of Marburg, Institut Gustave Roussy, German Breast Group, CHU de Québec-Laval
    Duration: 2020-2022
  4. Project Title: “Liquid biopsies for the identification of mechanisms of resistance to PARP inhibitors in BRCA1/2-associated cancers” (654/C/2019)
    Coordinator: Violeta Serra
    Funding Agency: La Marató TV3
    Partner Institutions: IRB Lleida
    Duration: 2020-2022
  5. Project Title: “Modulation of androgen receptor signalling as a therapeutic strategy for oestrogen receptor-positive metastatic breast cancer” (2018NovPCC1291)
    Principal Investigator: Violeta Serra
    Funding Agency: Breast Cancer Now- Catalyst
    Duration: 2019-2021
  6. Project Title: “PARPiPRED: a companion diagnostic test to enable personalized medicine in cancer” (CaixaImpulse Consolidate, CF91-00008)
    Principal Investigator: A. Llop
    Funding Agency: La Caixa Foundation
    Duration: 2020-2021
  7. Project Title: “Clinical Qualification of DNA Repair Defects as Biomarkers in Metastatic Prostate Cancer Using Integrated Genomics and Tissue-Based Functional Assays” (PC170510P1)
    Coordinators: J. Mateo
    Funding Agency: Department of Defense, USA
    Duration: 2018-2021
  8. Project Title: “MESI-STRAT: Systems Medicine of Metabolic-Signaling Networks-A New Concept for Breast Cancer Patient Stratification” (754688)
    Call: H2020-SC1-2016-2017 (Personalised Medicine)
    Topic: SC1-PM-02-2017
    Coordinator: Prof. K. Thedieck, UMCG, NL
    Funding Agency: European Commission
    Duration: 2018-2022