We focus on the molecular pathophysiology of pancreatic ductal adenocarcinoma (PDAC) and bladder carcinoma taking a disease-oriented approach. These tumours present very distinct clinical challenges. We learn from patient samples, cultured cells/organoids, and genetically modified mice. To translate the findings, we bring this knowledge to a “population” level – leveraging on information and samples from large patient cohorts – together with Núria Malats (CNIO).
PDAC has a dismal prognosis even when diagnosed early. We aim at dissecting the molecular mechanisms involved in very early steps of tumour development, harnessing the power of mouse genetic editing. A main hypothesis is that cell differentiation is an early and potent tumour suppressor mechanism. Understanding the contribution of early molecular events is crucial to design better strategies for prevention and early tumour detection.
Bladder cancer presents with a very wide clinical and pathological heterogeneity. We aim at acquiring knowledge about the underlying biology that might be leveraged towards improved tumour subclassification, prediction of outcome, and therapy.
Publications
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King SD, Veliginti S, Brouwers MCGJ, Ren Z, Zheng W, Setiawan VW, Wilkens LR, Shu XO, Arslan AA, Beane Freeman LE, Bracci PM, Canzian F, Du M, Gallinger SJ, Giles GG, Goodman PJ, Haiman CA, Kogevinas M, Kooperberg C, LeMarchand L, Neale RE, Visvanathan K, White E, Albanes D, Andreotti G, Babic A, Berndt SI, Brais LK, Brennan P, Buring JE, Rabe KG, Bamlet WR, Chanock SJ, Fuchs CS, Gaziano JM, Giovannucci EL, Hackert T, Hassan MM, Katzke V, Kurtz RC, Lee IM, Malats N, Murphy N, Oberg AL, Orlow I, Porta M, Real FX, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Yu H, Zeleniuch-Jacquotte A, Yu K, Wolpin BM, Duell EJ, Li D, Hung RJ, Perdomo S, McCullough ML, Freedman ND, Patel AV, Peters U, Riboli E, Sund M, Tjønneland A, Zhong J, Van Den Eeden SK, Kraft P, Risch HA, Amundadottir LT, Klein AP, Stolzenberg-Solomon RZ, Antwi SO. (2023).Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization. Cancer Epidem Biomar 32, 1265-1269. CNIO Publication.
Suarez-Cabrera C, Estudillo L, Ramón-Gil E, Martínez-Fernández M, Peral J, Rubio C, Lodewijk I, Martín de Bernardo Á, García-Escudero R, Villacampa F, Duarte J, de la Rosa F, Castellano D, Guerrero-Ramos F, Real FX, Malats N, Paramio JM, Dueñas M (2022).BlaDimiR: A Urine-based miRNA Score for Accurate Bladder Cancer Diagnosis and Follow-up. Eur Urol 82, 663-667. CNIO Publication.
Molina-Montes E, Coscia C, Gómez-Rubio P, Fernández A, Rianne Boenink R, Rava M, Márquez M, Molero X, Löhr M, Sharp L, Michalski CW, Farré A, Perea J, O'Rorke M, Greenhalf W, Iglesias M, Tardón A, Gress T, Barberà VM, Crnogorac-Jurcevic T, Muñoz-Bellvís L, Domínguez-Muñoz E, Harald Renz H, Balsells J, Costello E, Ilzarbe L, Jörg Kleeff J, Kong B, Mora J, O'Driscoll D, Poves I, Scarpa A, Yu J, Hidalgo M, Lawlor RT, Ye W, Carrato A, Real FX, Malats N, on behalf of the PanGenEU Study Investigators (2021).Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes, and obesity/BMI through causal inference and mediation analyses.. Gut 70, 319-329. CNIO Publication.
Lindskrog SV, Prip F, Lamy P, Taber A, Groeneveld CS, Birkenkamp-Demtröder K, Jensen JB, Strandgaard T, Nordentoft I, Christensen E, Sokac M, Birkbak NJ, Maretty L, Hermann GG, Petersen AC, Weyerer V, Grimm MO, Horstmann M, Sjödahl G, Höglund M, Steiniche T, Mogensen K, de Reyniès A, Nawroth R, Jordan B, Lin X, Dragicevic D, Ward DG, Goel A, Hurst CD, Raman JD, Warrick JI, Segersten U, Sikic D, van Kessel KEM, Maurer T, Meeks JJ, DeGraff DJ, Bryan RT, Knowles MA, Simic T, Hartmann A, Zwarthoff EC, Malmström PU, Malats N, Real FX, Dyrskjøt L (2021).An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nat Commun 1, 2301. CNIO Publication. Open Access
Jermusyk A, Zhong J, Connelly KE, Gordon N, Perera S, Abdolalizadeh E, Zhang T, O'Brien A, Hoskins JW, Collins I, Eiser D, Yuan C; PanScan Consortium; PanC4 Consortium, Risch HA, Jacobs EJ, Li D, Du M, Stolzenberg-Solomon RZ, Klein AP, Smith JP, Wolpin BM, Chanock SJ, Shi J, Petersen GM, Westlake CJ, Amundadottir LT (2021).A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer. Am J Hum Genet 108, 1852-1865. CNIO Publication.
López de Maturana E, Rodríguez JA, Alonso L, Lao O, Molina-Montes E, Martín-Antoniano IA, Gómez-Rubio P, Lawlor R, Carrato A, Hidalgo M, Iglesias M, Molero X, Löhr M, Michalski C, Perea J, O'Rorke M, Barberà VM, Tardón A, Farré A, Muñoz-Bellvís L, Crnogorac-Jurcevic T, Domínguez-Muñoz E, Gress T, Greenhalf W, Sharp L, Arnes L, Cecchini L, Balsells J, Costello E, Ilzarbe L, Kleeff J, Kong B, Márquez M, Mora J, O'Driscoll D, Scarpa A, Ye W, Yu J; PanGenEU Investigators, García-Closas M, Kogevinas M, Rothman N, Silverman DT; SBC/EPICURO Investigators, Albanes D, Arslan AA, Beane-Freeman L, Bracci PM, Brennan P, Bueno-de-Mesquita B, Buring J, Canzian F, Du M, Gallinger S, Gaziano JM, Goodman PJ, Gunter M, LeMarchand L, Li D, Neale RE, Peters U, Petersen GM, Risch HA, Sánchez MJ, Shu XO, Thornquist MD, Visvanathan K, Zheng W, Chanock SJ, Easton D, Wolpin BM, Stolzenberg-Solomon RZ, Klein AP, Amundadottir LT, Marti-Renom MA, Real FX, Malats N (2021).A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer. Genome Med 13, 15. CNIO Publication. Open Access
Vangala D, Ladigan S, Liffers ST, Noseir S, Maghnouj A, Götze TM, Verdoodt B, Klein-Scory S, Godfrey L, Zowada MK, Huerta M, Edelstein DL, de Villarreal JM, Marqués M, Kumbrink J, Jung A, Schiergens T, Werner J, Heinemann V, Stintzing S, Lindoerfer D, Mansmann U, Pohl M, Teschendorf C, Bernhardt C, Wolters H, Stern J, Usta S, Viebahn R, Admard J, Casadei N, Fröhling S, Ball CR, Siveke JT, Glimm H, Tannapfel A, Schmiegel W, Hahn SA (2021).Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models.. Genome Med 13, 116. CNIO Publication.
Rosato V, Gómez-Rubio P, Molina-Montes E, Márquez M, Löhr M, O'Rorke M, Michalski CW, Molero X, Farré A, Perea J, Kleeff J, Crnogorac-Jurcevic T, Greenhalf W, Ilzarbe L, Tardón A, Gress T, Barberá VM, Domínguez-Muñoz E, Muñoz-Bellvís L, Balsells J, Costello E, Iglesias M, Kong B, Mora J, O'Driscoll D, Poves I, Scarpa A, Ye W, Hidalgo M, Sharp L, Carrato A, Real FX, La Vecchia C, Malats N; PanGenEU Study Investigators. (2021).Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study. Eur J Cancer Prev 30, 423-430. CNIO Publication.
Kamoun A, Reyniès A, Allory Y, Sjödahl G, Gordon Robertson A, Seiler R, Hoadley KA, Groeneveld CS, Al-Ahmadie H, Choi W, Castro MAA, Fontugne J, Eriksson P, Mo Q, Kardos J, Zlotta A, Hartmann A, Dinney CP, Bellmunt J, Powles T, Malats N, Chan KS, Kim WY, McConkey DJ, Black PC, Dyrskjøt L, Höglund M, Lerner SP, Real FX, Radvanyi F; Bladder Cancer Molecular Taxonomy Group (2020).A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. Eur Urol 77, 420-423. CNIO Publication. Open Access
van Rhijn BWG, Mertens LS, Mayr R, Bostrom PJ, Real FX, Zwarthoff EC, Boormans JL, Abas C, van Leenders GJLH, Götz S, Hippe K, Bertz S, Neuzillet Y, Sanders J, Broeks A, van der Heijden MS, Jewett MAS, Marquez M, Stoehr R, Zlotta AR, Eckstein M, Soorojebally Y, Roshani H, Burger M, Otto W, Radvanyi F, Sirab N, Wullich PD, van der Kwast TH*, Malats N*, Hartmann A*, Allory Y*, Zuiverloon TCM* (2020).FGFR3 mutation status and FGFR3 expression in a Large Bladder Cancer Cohort treated by Radical Cystectomy: Implications for anti-FGFR3 Treatment?. Eur Urol 78, 682-687. CNIO Publication.
Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, Song L, Arslan AA, Beane Freeman LE, Bracci P, Canzian F, Du M, Gallinger S, Giles GG, Goodman PJ, Kooperberg C, Le Marchand L, Neale RE, Rosendahl J, Scelo G, Shu XO, Visvanathan K, White E, Zheng W, Albanes D, Amiano P, Andreotti G, Babic A, Bamlet WR, Berndt SI, Brennan P, Bueno-de-Mesquita B, Buring JE, Campbell PT, Chanock SJ, Fuchs CS, Gaziano JM, Goggins MG, Hackert T, Hartge P, Hassan MM, Holly EA, Hoover RN, Katzke V, Kirsten H, Kurtz RC, Lee IM, Malats N, Milne R, Murphy N, Ng K, Oberg AL, Porta M, Rabe KG, Real FX, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Wilkens LR, Yu H, Zeleniuch-Jacquotte A, Shi J, Duell EJ, Amundadottir LT, Li D, Petersen GM, Wolpin BM, Risch HA, Yu K, Klein AP, Stolzenberg-Solomon R (2020).Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk. Cancer Res 80, 4004-4013. CNIO Publication.
Molina-Montes E, Van Hoogstraten L, Gomez-Rubio P, Löhr M, Sharp L, Molero X, Márquez M, Michalski CW, Farré A, Perea J, O'Rorke M, Greenhalf W, Ilzarbe L, Tardon A, Gress TM, Barberà VM, Crnogorac-Jurcevic T, Muñoz-Bellvis L, Domínguez-Muñoz E, Balsells J, Costello E, Iglesias M, Kleeff J, Kong B, Mora J, O'Driscoll D, Poves I, Scarpa A, Yu J, Ye W, Hidalgo M, Carrato A, Lawlor R, Real FX, Malats N; PanGenEU Study Investigators. (2020).Pancreatic Cancer Risk in Relation to Lifetime Smoking Patterns, Tobacco Type, and Dose-Response Relationships. Cancer Epidem Biomar 29, 1009-1018. CNIO Publication.
Prades J, Arnold S, Brunner T, Cardone A, Carrato A, Coll-Ortega C, De Luze S, Garel P, Goossens M, Grilli R, Harris M, Louage M, Malats N, Partelli S, Pastorekova S, Petrulionis M, Price R, Sclafani F, Smolkova B, Borras JM (2020).The Bratislava Statement: consensus recommendations for improving pancreatic cancer care.. ESMO OPEN 5, e001051. CNIO Publication.
Open Access