19th Ave New York, NY 95822, USA

Grup d'Expressió Gènica i Càncer

Gene Expression and Cancer Group VHIO

Estudiem tumors cerebrals primaris i metàstasis cerebrals, que són alguns dels càncers més agressius. Tant el glioblastoma com la metàstasi cerebral són malalties molt greus amb opcions terapèutiques limitades. Per això, és fonamental avançar en aquest camp per millorar els resultats d’aquests pacients.

L’evolució de l’heterogeneïtat és un dels principals reptes que actualment obstaculitzen els nostres esforços per tractar amb més eficàcia els càncers cerebrals. Ens centrem en l’heterogeneïtat i l’evolució intertumorals, cosa que inclou l’heterogeneïtat genòmica, les cèl·lules iniciadores del càncer i l’heterogeneïtat de les cèl·lules immunitàries o de l’estroma, inclòs l’estudi de TGF-β i LIF.

Els tumors estan compostos per un mosaic de subclons cel·lulars que difereixen en les seves alteracions genòmiques. Explorem la diversitat genòmica present en el glioblastoma i analitzem l’heterogeneïtat genòmica intratumoral a mesura que evoluciona amb el temps en resposta a la teràpia.

El nostre grup està dissenyant eines per monitoritzar l’evolució de l’heterogeneïtat genòmica i estudiar l’ús de biòpsies líquides per al càncer cerebral mitjançant l’estudi de l’ADN tumoral lliure de cèl·lules circulants al líquid cefalorraquidi dels pacients. En concret, suggerim que s’utilitzi el líquid cefalorraquidi com a biòpsia líquida per a la vigilància en temps real del càncer cerebral més a prop de la clínica.

Joan Seoane
Cap de grup
  • Identificar noves dianes terapèutiques contra els tumors cerebrals i nous biomarcadors per predir amb més precisió la resposta a la teràpia.
  • Estudiar l’heterogeneïtat intratumoral.
  • Investigar el microambient tumoral.
  • Desenvolupar mètodes de diagnòstic molecular no invasiu mitjançant l’estudi de biomarcadors circulants.
  • Generar models murins de càncer cerebral derivats de pacients.

Figura: Biòpsies líquides en el tumor cerebral més comú en els infants.

Gene Expression and Cancer Group VHIO
Cap de grup
Joan Seoane
Personal científic
Ignasi Barba
Becaris postdoctorals
Ester Bonfill
Raffaella Iurlaro
Gonçalo Rodrigues
Becària de recerca
Simona Casalino
Estudiant de màster
Samia Hajem
Estudiant de postgrau
María López
Tècniques
Alexandra Arias
Isabel Cuartas
Iris Marcote
Almudena Neva
Bioinformàtic

Publicacions científiques més rellevants

  • Rubio-Perez C, Planas-Rigol E, Trincado JL, Bonfill-Teixidor E, Arias A, Marchese D, Moutinho C, Serna G, Pedrosa L, Iurlaro R, Martínez-Ricarte F, Escudero L, Cordero E, Cicuendez M, Ruiz S, Parra G, Nuciforo P, Gonzalez J, Pineda E, Sahuquillo J, Tabernero J, Heyn H*, Seoane J*. Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment. Nature Communications. 2021
  • Escudero L, Llort A, Arias A, Diaz-Navarro A, Martínez-Ricarte F, Rubio-Perez C, Mayor R, Caratú G, Martínez-Sáez E, Vázquez-Méndez É, Lesende-Rodríguez I, Hladun R, Gros L, Ramón y Cajal S, Poca M, Puente X, Sahuquillo J, Gallego S, Seoane J. Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma. Nature Communications. 2020; 11(1):5376.
  • Bobillo S, Crespo M, Escudero L, Mayor R, Raheja P, Carpio C, Rubio-Perez C, Tazón-Vega B, Palacio C, Carabia J, Jiménez I, Nieto JC, Montoro J, Martínez-Ricarte F, Castellví J, Simó M, Puigdefàbregas L, Abrisqueta P, Bosch F, Seoane J. Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. Haematologica. 2020. 106(2):513-521
  • Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, Rubio-Perez C, Iurlaro R, Arias A, Cuartas I, Sala-Hojman A, Escudero E, Martínez-Ricarte F, Huber-Ruano I, Nuciforo P, Pedrosa L, Marques C, Braña I, Garralda E, Vieito M, Squatrito M, Pineda E, Graus F, Espejo C, Sahuquillo J, Tabernero J, Seoane J. LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8 + T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun. 2019 Jun 11;10(1):2416.
  • Martínez-Ricarte F, Mayor R, Martínez-Sáez E, Rubio-Pérez C, Pineda E, Cordero E, Cicuéndez M, Poca MA, López-Bigas N, Ramon y Cajal S, Vieito M, Carles J, Tabernero J, Vivancos A, Gallego S, Graus F, Sahuquillo J, Seoane J. Molecular diagnosis of diffuse gliomas through sequencing of cell-free circulating tumour DNA from cerebrospinal fluid. Clin Cancer Res. 2018 Jun 15;24(12):2812-2819.
  • Capdevila J, Mayor R, Mancuso FF, Iglesias C, Caratù G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Álvarez 4, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J. Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol. 2018 June 1; 29(6): 1454–1460.
  • Seoane J. Division hierarchy leads to cell heterogeneity. Nature. 2017 Sep 14;549(7671):164-166.
  • Huber-Ruano I, Raventos C, Cuartas I, Sánchez-Jaro C, Wosikowski K, Janicot M, Seoane J. An Antisense oligonucleotide targeting TGF-β2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages. Ann Oncol. 2017 Sep 1;28(9):2278-2285
  • Seoane J, Gomis RR. TGFβ Family Signaling in Tumor Suppression and Cancer Progression. Cold Spring Harb Perspect Biol. 2017 Dec 1;9(12).
  • 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.
  • Gueorguieva I, Cleverly A, Desaiah D, Azaro A, Seoane J, Braña I, Sicart E, Miles C, Lahn MM, Mitchell MI, Rodon J. Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.  Drugs Context. 2016 Dec 2;5:212303. eCollection 2016.
  • De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J*. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nature Communications. 2015; 6:8839. (*corresponding author).
  • Rodon L, Gonzalez-Junca A, Inda MD, Sala-Hojman A, Martinez-Saez E, Seoane J*. Active CREB1 promotes a malignant TGF-β2 autocrine loop in glioblastoma. Cancer Discov. 2014; 4(10):1230-41. (*corresponding author).
  • Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratu 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 of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation. Cancer Discov. 2013; 3(11):1238-44 (*co-corresponding authors).
  • Eichhorn PJ, Rodon L, Gonzàlez-Juncà A, Dirac A, Gili M, Martínez-Sáez E, Aura C, Barba I, Peg V., Prat A., Cuartas I, Jimenez J, García-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane J. USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma. Nature Medicine 2012;18(3):429-35. [see News and Views: Aggarwal K and Massagué J. Ubiquitin removal in the TGF- β pathway. Nature Cell Biology. 2012;14(7):656-7].
  • Anido J, Sáez-Borderías A, Gonzàlez-Juncà A, Rodón L, Folch G, Carmona MA, Prieto-Sánchez RM, Barba I, Martínez-Sáez E, Prudkin L, Cuartas I, Raventós C, Martínez-Ricarte F, Poca MA, García-Dorado D, Lahn M, Yingling J, Rodón J, Sahuquillo J, Baselga J, Seoane J. TGF-β receptor inhibitors target the CD44high/Id1high glioma-initiating cell population in human glioblastoma. Cancer Cell. 2010;18(6):655-68 [see Preview: Edwards LA, Fine HA. The Ids have it. Cancer Cell. 2010;18(6):543-5.

Totes les publicacions

  • Soffietti R, Bettegowda C, Mellinghoff IK, Warren KE, Ahluwalia MS, De Groot JF, Galanis E, Gilbert MR, Jaeckle KA, Le Rhun E, Rudà R, Seoane J, Thon N, Umemura Y, Weller M, van den Bent MJ, Vogelbaum MA, Chang SM, Wen PY. Liquid biopsy in gliomas: a RANO review and proposals for clinical applications. Neuro Oncol. 2022. (Online ahead of print).
  • Seoane J, Escudero L. Cerebrospinal fluid liquid biopsies for medulloblastoma. Nature Reviews Clinical Oncology. 2022;19(2):73-74.
  • Gulley JL, Schlom J, Barcellos-Hoff MH, Wang XJ, Seoane J, Audhuy F, Lan Y, Dussault I, Moustakas A. Dual inhibition of TGF-β and PD-L1 as a novel cancer treatment approach. Molecular Oncology.2021. (Online ahead of print).
  • Nieto P, Elosua-Bayes M, Trincado JL, Marchese D, Massoni-Badosa R, Salvany M, Henriques A, Nieto J, Aguilar-Fernández S, Mereu E, Moutinho C, Ruiz S, Lorden P, Chin VT, Kaczorowski D, Chan CL, Gallagher R, Chou A, Planas-Rigol E, Rubio-Perez C, Gut I, Piulats JM, Seoane J, Powell JE, Batlle E, Heyn H. A single-cell tumor immune atlas for precision oncology. Genome Res. 2021; (10):1913-1926.
  • Le Rhun E, Guckenberger M, Smits M, Dummer R, Bachelot T, Sahm F, Galldiks N, de Azambuja E, Berghoff AS, Metellus P, Peters S, Hong Y-K, Winkler F, Schadendorf D, van den Bent M, Seoane J, Stahel R, Minniti G, Wesseling P, Weller M & Preusser M on behalf of the EANO Executive Board and ESMO Guidelines Committee*. EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumors. Annals of Oncology. 2021; 32(11): 1332-1347.
  • Escudero L , Martínez-Ricarte F, Seoane J. ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer. Cancers. 2021; 13 (9):1989.
  • Rubio-Perez C, Planas-Rigol E, Trincado JL, Bonfill-Teixidor E, Arias A, Marchese D, Moutinho C, Serna G, Pedrosa L, Iurlaro R, Martínez-Ricarte F, Escudero L, Cordero E, Cicuendez M, Ruiz S, Parra G, Nuciforo P, Gonzalez J, Pineda E, Sahuquillo J, Tabernero J, Heyn H*, Seoane J*. Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment. Nature Communications. 2021 (Epub ahead of print).
  • Milena Cribiù F, Erra R, Pugni L, Rubio Perez C, Alonso L, Simonetti S, Croci GA, Serna G, Ronchi A, Pietrasanta C, Lunghi G, Fagnani AM, Pinana M, Matter M, Tzankov A, Terracciano L, Anton Pagarolas A, Ferrazzi E, Ferrero S, Iurlaro E, Seoane J*, Nuciforo P*. Severe SARS-CoV-2 placenta infection can impact neonatal outcome in the absence of vertical transmission. (*co-corresponding authors). Journal of Clinical Investigation. 2021 (Epub ahead of print).
  • Galson JD, Schaetzle S, Bashford-Rogers RJM, Raybould MIJ, Kovaltsuk A, Kilpatrick GJ, Minter R, Finch DK, Dias J, James LK, Thomas G, Jason Lee WY, Betley J, Cavlan O, Leech A, Deane CM, Seoane J, Caldas C, Pennington DJ, Pfeffer PE, Osbourn J. Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures. Frontiers in Immunology. 2020; 11:605170.
  • Ligero Hernández M, Garcia Ruiz A, Viaplana C, Villacampa Javierre G, Raciti MV, Landa J, Matos I, Martin Liberal JJ, Ochoa de Olza M, Hierro C, Mateo J, Gonzalez Rodriguez M, Morales R, Suárez C, Rodon J, Élez E, Braña I, Muñoz Couselo E, Oaknin A, Fasani R, Nuciforo P, Gil D, Rubio-Pérez C, Seoane J, Felip E, Escobar M, Tabernero J, Carles J, Dienstmann R, Garralda E, Perez Lopez R. A CT-based Radiomics Signature Is Associated with Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors. Radiology. 2021 Epub ahead of print.
  • Puyol M, Seoane J, Aguilar E, Vozza LB, Orbe I, Crawford KH, Fernández A, Bray F, Johnson SE, Gopal S. WORLD CANCER RESEARCH DAY: A call to action for a coordinated international research effort to prevent, diagnose and treat cancer. Clinical Cancer Research. 2021. 27(4):963-966.
  • Escudero L, Martínez-Ricarte F, Seoane J. Cerebrospinal fluid circulating tumour DNA as a liquid biopsy for central nervous system malignancies. Current Opinion Neurology. 2020; 33(6):736-741.
  • Escudero L, Llort A, Arias A, Diaz-Navarro A, Martínez-Ricarte F, Rubio-Perez C, Mayor R, Caratú G, Martínez-Sáez E, Vázquez-Méndez É, Lesende-Rodríguez I, Hladun R, Gros L, Ramón y Cajal S, Poca M, Puente X, Sahuquillo J, Gallego S, Seoane J. Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma. Nature Communications. 2020; 11(1):5376.
  • Jiménez, I, Carabia J, Bobillo S, Palacio C, Abrisqueta P, Pagès C, Nieto JC, Castellví J, Martínez‑Ricarte F, Escoda L, Perla C, Céspedes-Torrez DH, Boix J, Purroy N, Puigdefàbregas L, Seoane J, Bosch F, Crespo M. Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition. Journal of Neuro-Oncology. 2020; 149(1):13-25.
  • Ciardiello D, Elez ME, Tabernero J, Seoane J. Clinical development of therapies targeting TGFβ: current knowledge and future perspectives. Annals of Oncology. 2020. 31 (10):1336 – 1349.
  • Le Rhun E, Seoane J, Salzet M, Soffietti R, Weller M. Liquid biopsies for diagnosing and monitoring primary tumors of the central nervous system. Cancer letters. 2020; 480:24-28.
  • Seoane J. Immunotherapy Research: today’s science is tomorrow’s medicine. The Innovation Platform. 2020; 1: 122-123.
  • Bobillo S, Crespo M, Escudero L, Mayor R, Raheja P, Carpio C, Rubio-Perez C, Tazón-Vega B, Palacio C, Carabia J, Jiménez I, Nieto JC, Montoro J, Martínez-Ricarte F, Castellví J, Simó M, Puigdefàbregas L, Abrisqueta P, Bosch F, Seoane J. Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. Haematologica. 2020. 106(2):513-521
  • Gargini R*, Segura-Collar B*, Herránz B, Garcia-Escudero V, Romero-Bravo A, Núñez FJ, García-Pérez D, Gutiérrez-Guamán J, Ayuso-Sacido A, Seoane J, Pérez-Núñez A, Sepúlveda-Sánchez JM, Hernández-Laín A, Castro MG, García-Escudero R, Ávila J, Sánchez-Gómez P. The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas. Science Translational Medicine. 2020; 12(527)
  • Janin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P, Soler M, Nachmani D, Pelletier J, Schumann U, Calleja-Cervantes ME, Moran S, Guil S, Bueno-Costa A, Piñeyro D, Perez-Salvia M, Rosselló-Tortella M, Piqué L, Bech-Serra JJ, De La Torre C, Vidal A, Martínez-Iniesta M, Martín-Tejera JF, Villanueva A, Arias A, Cuartas I, Aransay AM, La Madrid AM, Carcaboso AM, Santa-Maria V, Mora J, Fernandez AF, Fraga MF, Aldecoa I, Pedrosa L, Graus F, Vidal N, Martínez-Soler F, Tortosa A, Carrato C, Balañá C, Boudreau MW, Hergenrother PJ, Kötter P, Entian KD, Hench J, Frank S, Mansouri S, Zadeh G, Dans PD, Orozco M, Thomas G, Blanco S, Seoane J, Preiss T, Pandolfi PP, Esteller M. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. Acta Neuropathologica. 2019;138(6):1053-1074.
  • Seoane J. Beyond blood with liquid biopsies. ESMO Perspectives. 2019 August 30.
  • Siravegna G, Mussolin B, Venesio T, Marsoni S, Seoane J, Dive C, Papadopoulos N, Kopetz S, Corcoran R. B, Siu L. L, and Bardelli A. How liquid biopsies can change clinical practice in oncology. Annals of Oncology. 2019; 30(10):1580-1590.
  • Pascual-GarcíaM, Bonfill-TeixidorE, Planas-RigolE, Rubio-PerezC, IurlaroR,AriasA, Cuartas I, Sala-HojmanA, Escudero E, Martínez-Ricarte F, Huber-Ruano I, NuciforoP, PedrosaL, MarquesC, BrañaI, GarraldaE, VieitoM, SquatritoM, PinedaE, GrausF, EspejoC, SahuquilloJ, TaberneroJ, Seoane J. LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8+T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun. 2019 Jun 11;10(1):2416.
  • Seoane J, De Mattos-ArrudaL, Le RhunE, BardelliA, WellerM. Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases. Ann Oncol. 2019 Feb 1;30(2):211-218.
  • Siravegna G, Mussolin B, Venesio T, Marsoni S, Seoane J, Dive C, Papadopoulos N, Kopetz S, Corcoran RB, Siu LL, Bardelli A. How liquid biopsies can change clinical practice in oncology. Ann Oncol. 2019 Oct 1;30(10):1580-1590.
  • De Mattos-Arruda L, Sammut SJ, Ross EM, Bashford-Rogers R, Greenstein E, Markus H, Morganella S, Teng Y, Maruvka Y, Pereira B, Rueda OM, Chin SF, Contente-Cuomo T, Mayor R, Arias A, Ali HR, Cope W, Tiezzi D, Dariush A, Dias Amarante T, Reshef D, Ciriaco N, Martinez-Saez E, Peg V, Ramon Y Cajal S, Cortes J, Vassiliou G, Getz G, Nik-Zainal S, Murtaza M, Friedman N, Markowetz F, Seoane J, Caldas C. The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer. Cell Rep. 2019 May 28;27(9):2690-2708.
  • Seoane J. Division hierarchy leads to cell heterogeneity. Nature. 2017 Sep 14;549(7671):164-166.
  • Huber-Ruano I, Raventos C, Cuartas I, Sánchez-Jaro C, Wosikowski K, Janicot M, Seoane J. An Antisense oligonucleotide targeting TGF-β2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages. Ann Oncol. 2017 Sep 1;28(9):2278-2285
  • Seoane J, Gomis RR. TGFβ Family Signaling in Tumor Suppression and Cancer ProgressionCold Spring Harb Perspect Biol. 2017 Dec 1;9(12).
  • 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 xenograftsNat Rev Cancer. 2017 Apr;17(4):254-268.
  • Gueorguieva I, Cleverly A, Desaiah D, Azaro A, Seoane J, Braña I, Sicart E, Miles C, Lahn MM, Mitchell MI, Rodon J. Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.  Drugs Context. 2016 Dec 2;5:212303. eCollection 2016.
  • Seoane J. The Taming of the TAMsTrends Cell Biol. 2016 Aug;26(8):562-3.
  • Gomis R, Seoane JTGFβ Family Signaling in Tumor Suppression and Cancer Progression. Cold Harbor 2016. In press 2016
  • Byrne A, Alferez D, Amant F, Annibali D, Arribas J, Biankin A, Bruna A, Budinská E, Caldas C, Chang D, Clarke R, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek M, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer H, Peeper D, Pelicci PG, Piris A, Roman-Roman S, Rueda O, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L. Interrogating open issues in oncology and cancer precision medicine using Patient-Derived Xenograft models. Nature Review Cancer. In Press 2016
  • Gueorguieva I, Cleverly A, Desaiah D, Azaro A, Seoane J, Braña I, et al. Drugs in Context 2016; 5:201303. “Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer”, Drugs in Context, 2016; 5: 201303. DOI: 10.7573/dic.212303
  • Seoane JThe Taming of the TAMs. Trends in Cell Biology. Aug;26(8):562-3. doi: 10.1016/j.tcb.2016.06.007. Epub 2016 Jul 6.
  • De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, Martínez-Ricarte F, Torrejon D, Oliveira M, Arias A, Raventos C, Tang J, Guerini-Rocco E, Martínez-Sáez E, Lois S, Marín O, de la Cruz X, Piscuoglio S, Towers R, Vivancos A, Peg V, Ramon y Cajal S, Carles J, Rodon J, González-Cao M, Tabernero J, Felip E, Sahuquillo J, Berger MF, Cortes J, Reis-Filho JS, Seoane J*Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nature Communications. 2015; 6:8839. (*corresponding author).
  • De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, Losurdo A, Pérez-Garcia J, Masci G, Corsi F, Cortés J, Seoane J, Calin GA, Santarpia L. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget. 2015;6(35):37269-80.
  • Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG 2nd, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015;5(11):1164-77
  • Iyengar PV, Jaynes P, Rodon L, Lama D, Law KP, Lim YP, Verma C, Seoane J, Eichhorn PJ. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Sci Rep. 2015;5:14733.
  • Ulloa F, Gonzàlez-Juncà A, Meffre D, Barrecheguren PJ, Martínez-Mármol R, Pazos I, Olivé N, Cotrufo T, Seoane J, Soriano E. Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth. PLoS One. 2015;10(3):e0119707.
  • Rodon J, Carducci MA, Sepulveda-Sanchez JM, Azaro A, Calvo E, Seoane J, Brana I, Sicart E, Gueorguieva I, Cleverly AL, Sokalingum Pillay N, Desaiah D, Estrem ST, Paz-Ares L, Holdoff M, Blakeley J, Lahn MM, Baselga J. First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma. Clin Cancer Res. 2015;21(3):553-60.
  • Rodon J, Carducci M, Sepulveda-Sánchez JM, Azaro A, Calvo E, Seoane J, Braña I, Sicart E, Gueorguieva I, Cleverly A, Pillay NS, Desaiah D, Estrem ST, Paz-Ares L, Holdhoff M, Blakeley J, Lahn MM, Baselga J. Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-β receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer. Invest New Drugs. 2015;33(2):357-70.
  • Seoane J*, De Mattos-Arruda L. Escaping out of the brain. Cancer Discov. 2014;4(11):1259-61. (*corresponding author)
  • Hidalgo M, Amant F, Biankin AV, Budinská E, Byrne AT, Caldas C, Clarke RB, de Jong S, Jonkers J, Mælandsmo GM, Roman-Roman S, Seoane J, Trusolino L, Villanueva A. Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research. Cancer Discov. 2014;4(9):998-1013.
  • Henderson D, Ogilvie LA, Hoyle N, Keilholz U, Lange B, Lehrach H on behalf of the OncoTrack Consortium. Personalized medicine approaches for colon cancer driven by genomics and systems biology: OncoTrack. Biotechnol J. 2014;9(9):1104-14.
  • Rodon L, Gonzalez-Junca A, Inda MD, Sala-Hojman A, Martinez-Saez E, Seoane J*Active CREB1 promotes a malignant TGF-β2 autocrine loop in glioblastoma. Cancer Discov. 2014;4(10):1230-41. (*corresponding author)
  • Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, Folch G, Gonzalez-Juncà A, Sodir NM, Masso-Vallés D, Beaulieu ME, Swigart LB, Mc Gee MM, Somma MP, Nasi S, Seoane J, Evan GI, Soucek L. Myc inhibition is effective against glioma and reveals a role for Myc in mitosis. Nature Communications. 2014;5:4632.
  • De Mattos-Arruda L, Weigelt B, Cortes J, Won HH, Ng CK, Nuciforo P, Bidard FC, Aura C, Saura C, Peg V, Piscuoglio S, Oliveira M, Smolders Y, Patel P, Norton L, Tabernero J, Berger MF, Seoane J, Reis-Filho JS. Capturing Intra-Tumor Genetic Heterogeneity by De Novo Mutation Profiling of Circulating Cell-Free Tumor DNA: A Proof-of-Principle. Ann Oncol. 2014;25(9):1729-35.
  • Martino-Echarri E, Fernández-Rodríguez R, Bech-Serra JJ, Plaza-Calonge MC, Vidal N, Casal C, Colomé N, Seoane J*, Canals F, Rodríguez-Manzaneque JC. Relevance of IGFBP2 proteolysis in glioma and contribution of the extracellular protease ADAMTS1Oncotarget. 2014;5(12):4295-304. (*corresponding author)
  • Seoane JGremlins Sabotage the Mechanisms of Cancer Stem Cell Differentiation. Cancer Cell. 2014;25(6):716-7.
  • Seoane J*, De Mattos-Arruda L. Brain metastasis: new opportunities to tackle therapeutic resistance. Review Article, Mol Oncol. 2014;8(6):1120-31. (*corresponding author).
  • Seoane J*, De Mattos-Arruda L. The challenge of intratumour heterogeneity in precision medicine. J Intern Med. 2014;276(1):41-51. (*corresponding author)
  • Inda MD, Bonavia R, Seoane J*. Glioblastoma multiforme: a look inside its heterogeneous nature. Cancers (Basel). 2014;6(1):226-39. (*co-corresponding author).
  • Cortés J, Calvo E, Vivancos A, Perez-Garcia J, Recio JA, Seoane JNew approach to cancer therapy based on a molecularly defined cancer classification. CA-Cancer J Clin. 2014;64(1):70-4.
  • De Mattos-Arruda L, Bidard FC, Won HH, Cortes J, Ng CK, Peg V, Nuciforo P, Jungbluth AA, Weigelt B, Berger MF, Seoane J*, Reis-Filho JS. Establishing the origin of metastatic deposits in the setting of multiple primary malignancies: The role of massively parallel sequencing. Mol Oncol. 2014;8(1):150-8 (*co-corresponding authors).
  • Serra V, Vivancos A, Puente XS, Felip E, Silberschmidt D, Caratu 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 of a Li-Fraumeni Syndrome patient with a novel HER2-V659E mutation. Cancer Discov. 2013;3(11):1238-44 (*co-corresponding authors).
  • De Mattos-Arruda L, Cortes J, Santarpia L, Vivancos A, Tabernero J, Reis-Filho JS, Seoane JCirculating Tumor Cells and Cell-Free DNA as Tools for Managing Breast Cancer. Nature Reviews. Clinical Oncology. 2013;10(7):377-89.
  • De Mattos-Arruda L, Tabernero J, Seoane J, Cortes J. Circulating tumour cells in early breast cancer. Lancet Oncol. 2012;13(9):e370.
  • Ros-Blanco L, Anido J, Bosser R, Este J, Clotet B, Kosoy A, Ruiz-Avila L, Teixido J, Seoane J*, Borrell JI. NonCyclam Tetraamines inhibit CXC Chemokine Receptor Type 4 and target Glioma-Initiating Cells. J Med Chem. 2012;55(17):7560-70 (*co-corresponding author).
  • Eichhorn PJ, Rodon L, Gonzàlez-Juncà A, Dirac A, Gili M, Martínez-Sáez E, Aura C, Barba I, Peg V., Prat A., Cuartas I, Jimenez J, García-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane JUSP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma. Nature Medicine 2012;18(3):429-35. [see News and Views: Aggarwal K and Massagué J. Ubiquitin removal in the TGF- β pathway. Nature Cell Biology. 2012;14(7):656-7].
  • Anido J, Sáez-Borderías A, Gonzàlez-Juncà A, Rodón L, Folch G, Carmona MA, Prieto-Sánchez RM, Barba I, Martínez-Sáez E, Prudkin L, Cuartas I, Raventós C, Martínez-Ricarte F, Poca MA, García-Dorado D, Lahn M, Yingling J, Rodón J, Sahuquillo J, Baselga J, Seoane JTGF-β receptor inhibitors target the CD44high/Id1high glioma-initiating cell population in human glioblastoma. Cancer Cell. 2010;18(6):655-68 [see Preview: Edwards LA, Fine HA. The Ids have it. Cancer Cell. 2010;18(6):543-5.
  • Seoane JNO Signals from the Cancer Stem Cell Niche. Cell Stem Cell. 2010;6(2):97-8.
  • Seoane JTGF-β and cancer initiating cellsCell Cycle. 2009;8(23):3787-8.
  • Santamaria-Martínez A, Barquinero J, Barbosa-Desongles A, Hurtado A, Pinós T, Seoane J, Poupon MF, Morote J, Reventós J, Munell F. Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis. Exp Cell Res. 2009 ;315(17):3004-13.
  • Peñuelas S, Anido J, Prieto-Sánchez RM, Folch G, Barba I, Cuartas I, García-Dorado D, Poca MA, Sahuquillo J, Baselga J, Seoane JTGF-β increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma. Cancer Cell. 2009;15(4):315-27 [see Preview: Fine HA. Glioma stem cells: not all created equal. Cancer Cell. 2009;15(4):247-9].
  • Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, Baselga J. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3- kinase inhibitor NVP-BEZ235. Cancer Res. 2008;68(22):9221-30.
  • Seoane JThe TGF-β pathway as a therapeutic target in cancer. Clin Transl Oncol. 2008;10(1):14-19.
  • Baselga J, Rothenberg ML, Tabernero J, Seoane J, Daly T, Cleverly A, Berry B, Rhoades SK, Ray CA, Fill J, Farrington DL, Anne L, Yingling JM, Lahn M, Arteaga C, Carducci M. TGF-β signaling related markers in cancer patients with bone metastasis. Biomarkers. 2008;13(2):217-36.
  • Seoane JTGF-β signaling in homeostasis and cancer. In: Jakowlew SB (ed.) Cancer Drug Discovery and Development: Transforming Growth Factor-Beta in Cancer Therapy, Vol. 1: Basic and Clinical Biology . 1st ed. Totowa, NJ: Humana Press; 2008. pp 23-35.
  • Bruna A, Darken RS, Rojo F, Ocaña A, Peñuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J, Seoane JHigh TGF-β-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 2007;11,147-160 [see Preview: Kesari S, Jackson-Grusby L, Stiles CD. “Smad”eningly erratic: target gene methylation determines whether TGFbeta promotes or suppresses malignant glioma. Dev Cell. 2007;12(3):324-5.].
  • Gomis RR, Alarcón C, He W, Wang Q, Seoane J, Lash A and Massagué J. A FoxO-Smad synexpression group in human keratinocytes. P Natl Acad Sci USA. 2006;103(34):12747-52.
  • Seoane JEscaping from the TGF-β anti-proliferative control. Carcinogenesis. 2006;27(11):2148-56.
  • Massagué J, Seoane J, Wotton D. Smad Transcription Factors. Gene Dev. 2005;19,2783-2810.
  • Seoane J, Le H-V, Shen L, Anderson SA, Massagué J. Integration of Smad and Forkhead Pathways in the Control of Neuroepithelial and Glioblastoma Cell Proliferation. Cell. 2004;117,211-223 (Cover) [see Preview: Arden KC. FoxO: Linking new signaling pathways. Mol Cell. 2004;14(4):416-8].
  • Seoane Jp21(WAF1/CIP1) at the Switch Between the Anti-Oncogenic and Oncogenic Faces of TGF-β. Cancer Biol Ther. 2004;3(2):226-7.
  • Calonge J, Seoane J, Massagué J. Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-β. J Biol Chem. 2004;279(22):23759-65.
  • Seoane J, Le H-V, Massagué J. Myc suppression of p21Cip1 Cdk inhibitor determines the outcome of the p53 response to DNA damage. Nature. 2002;419(6908):729-34 [see Preview: Vousden KH. Switching from life to death: the Miz-ing link between Myc and p53. Cancer Cell. 2002;2(5):351-2].
  • Wu J-W, Hu M, Chai J, Seoane J, Huse M, Li C, Kyin S, Fairman R, Muir TW, Massague J, Shi Y. Crystal structure of a phosphorylated Smad2: Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-β signaling. Mol Cell. 2001;8(6):1277-89.
  • Seoane J, Pouponnot C, Staller P, Schader M, Eilers M, Massagué J. TGF-β influences Myc, Miz-1 and Smad to control the CDK inhibitor p15Ink4b. Nature Cell Biology. 2001;3(4):400-8.
  • Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massagué J, Hanel F, Eilers M. Repression of p15Ink4b expression by Myc through association with Miz-1. Nature Cell Biology. 2001;3,392-399.
  • Hata A, Seoane J, Lagna G, Montalvo E, Hemmati-Brivanlou A, Massagué J.  OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell. 2000;100(2):229-40.
  • De la Iglesia N, Mukhtar M, Seoane J, Guinovart JJ, Agius L. The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. J Biol Chem. 2000;275(14):10597-603.
  • Warner BJ, Blain SW, Seoane J, Massagué J. Myc downregulation by transforming growth factor beta required for activation of the p15 Ink4b G1 arrest pathway. Mol Cell Biol. 1999;19(9):5913-22.
  • Seoane J, Barberà A, Telemaque-Potts S, Newgard SB, Guinovart JJ. Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male zucker diabetic fatty rats. J Biol Chem. 1999;274(45):31833-8.
  • Seoane J, Trinh K, O’Doherty RM, Gómez-Foix AM, Lange AJ, Newgard CB, Guinovart JJ. Metabolic impact of adenovirus-mediated overexpression of the glucose 6-phosphatase catalytic subunit in hepatocytes. J Biol Chem. 1997;272(43):26972-7.
  • Guinovart JJ, Gómez-Foix AM, Seoane J, Fernández-Novell JM, Bellido D, Vilaró S. Bridging the gap between glucose phosphorylation and glycogen synthesis in the liverBiochem Soc T. 1997;25(1):157-60.
  • Seoane J, Gómez-Foix AM, O´Doherty RM, Gómez-Ara C, Newgard CB, Guinovart JJ. Glucose 6-phosphate produced by glucokinase, but not hexokinase I, promotes the activation of hepatic glycogen synthase. J Biol Chem. 1996;271(39):23756-60.
  • O’Doherty RM, Lehman DL, Seoane J, Gómez-Foix AM, Guinovart JJ, Newgard CB. Differential metabolic effects of adenovirus-mediated glucokinase and hexokinase I overexpression in rat primary hepatocytes. J Biol Chem. 1996;271(34):20524-30.
  1. Caracterización molecular de los tumores cerebrales pediátricos mediante el estudio del DNA circulante en sangre y líquido cefalorraquídeo – Fundación FERO
  2. Identificación de mecanismos de resistencia a tratamiento a través del estudio de la evolución de la heterogeneidad intra-tumoral en glioblastoma – Instituto de Salud Carlos III
  3. Study of the molecular mechanisms involved in primary (glioblastoma) and secondary (metastasis) brain tumors to identify novel therapeutic targets and anti-cancer agents, biomarkers to select treatments and novel non-invasive methods for molecular diagnosis – Asociación Española Contra el Cáncer (AECC)
  4. Programa joves i ciència-Laboratori Joan Seoane – Fundació Catalunya La Pedrera
  5. Desarrollo de un fármaco innovador y personalizado para el tratamiento del cáncer que reactiva el sistema inmune contra el tumor y elimina las células madre tumorales (expediente: RTC-2015-3771-1)
    Proyecto financiado por el Ministerio de Economía y Competitividad

    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.
  6. Identification of novel immunotherapeutic targets in lung and melanoma brain metastases – Fundación Ramón Areces