Durant l’última dècada, hem estat testimonis d’una revolució en el tractament del càncer de pròstata resistent a la castració metastàtic (CPRCm), que és una forma letal i avançada del càncer de pròstata. Gràcies a un coneixement més gran de les seves característiques biològiques subjacents, s’ha pogut desenvolupar una sèrie de compostos dirigits a la via de senyalització androgènica i el sistema immunitari, així com els taxans i els radiofàrmacs.
El nostre model de recerca segueix un model del laboratori a la pràctica i viceversa. Hem creat una plataforma per adquirir mostres longitudinals de pacients amb càncer de pròstata avançat, tant de teixit tumoral com de biòpsies líquides, que es puguin utilitzar per investigar les característiques evolutives de la malaltia, així com per generar models de laboratori de càncer de pròstata avançat derivats de pacients que puguem aprofitar per investigar noves estratègies terapèutiques al laboratori.
A més, la posada en marxa d’assajos clínics iniciats per investigadors és fonamental per a la nostra estratègia de recerca com a plataforma per a estudis correlatius que puguin optimitzar la via de desenvolupament de fàrmacs per a pacients amb càncer de pròstata. Actualment, som el laboratori central de dos assaigs clínics multicèntrics acadèmics, i també actuem com a repositori nacional del registre IRONMAN, una important iniciativa internacional per crear un gran banc de dades clíniques i bioespècimens de pacients amb càncer de pròstata metastàtic (CPm).
El nostre objectiu és integrar coneixements de biologia molecular, genòmica, transcriptòmica, ciències computacionals i dades clíniques per desenvolupar estratègies de medicina de precisió per a pacients amb càncer de pròstata. Per això, el nostre equip està format per científics biomèdics experts en biologia del càncer, genòmica i transcriptòmica, bioinformàtica i biòpsia líquida, així com per oncòlegs mèdics i gestors de dades clíniques.
Una de les nostres línies de recerca principals és desxifrar com s’adapta el càncer de pròstata a l’exposició a tractaments sistèmics, en particular els fàrmacs dirigits als andrògens, amb especial atenció a la regulació del cicle cel·lular i la resposta al dany de l’ADN i la aparició de fenotips quiescents i senescents que poden impulsar la resistència als fàrmacs. Mitjançant l’estudi de models in vitro i in vivo, inclosos els xenoempelts derivats de pacients (PDX) dels pacients que participen als nostres estudis clínics, pretenem atacar els fenotips emergents mitjançant combinacions de fàrmacs. Actualment, aquests estudis estan finançats amb subvencions del Ministeri de Sanitat espanyol, la Fundació FERO, l’Associació Espanyola Contra el Càncer (AECC) i mitjançant col·laboracions amb empreses biofarmacèutiques.
El nostre grup també persegueix la caracterització molecular del càncer de pròstata avançat, centrant-se en com els tumors evolucionen de manera heterogènia a mesura que adquireixen resistència a diferents tractaments. Per això, hem creat una plataforma de genòmica i transcriptòmica al laboratori per elaborar perfils d’ADN i ARN a partir de biòpsies de pacients. Estem desenvolupant nous assaigs de biòpsia líquida que ens permetran estudiar la malaltia a través de mostres longitudinals. Mitjançant l’explotació de conjunts de dades genòmiques d’accés públic de pacients a diferents estadis de la malaltia, els nostres científics computacionals investiguen com canvia el perfil genòmic de la malaltia al llarg del temps. Actualment, aquests estudis estan finançats per subvencions dels Programes de Recerca Mèdica Dirigits pel Congrés (CDMRP) del Departament de Defensa dels Estats Units (DoD), el Ministeri de Sanitat espanyol, la Fundació CRIS contra el Càncer, l’AECC , la Fundació FERO i la Fundació la Caixa.
Finalment, atès que les dades clíniques correlatives ben comentades són crucials per establir la possible rellevància de les dades moleculars, el nostre equip manté bases de dades que recullen les dades de resultats de tots els pacients que donen mostres per als nostres estudis per tal de fer anàlisis correlatives posteriors.
Per avançar més ràpidament en aquest camp, creiem en la ciència dequip. Per això, participem en diverses col·laboracions que uneixen recursos i combinen coneixements transfronterers de diversos equips i grups de recerca.
En resum, la nostra investigació integra diferents modalitats de dades generades al laboratori que poden portar al disseny d’intervencions terapèutiques destinades a millorar els resultats dels pacients amb càncer de pròstata.
- Investigar les correlacions entre el perfil molecular del pacient i el resultat clínic que puguin guiar estratègies de tractament del càncer de pròstata més precises.
- Estudiar com els càncers de pròstata s’adapten a la teràpia, centrant-se en les vulnerabilitats emergents per endarrerir la recurrència de la malaltia.
- Investigar l’heterogeneïtat del tumor en resposta a la teràpia en models de xenoempelt (PDX) preclínics i derivats del pacient, així com interrogant biòpsies de pacients.
- Desenvolupar noves eines de biòpsia líquida que es puguin fer servir per monitoritzar l’evolució del tumor.
- Aplicar canalitzacions computacionals per investigar les firmes genòmiques al càncer de pròstata.
- Desenvolupament d’assajos clínics acadèmics per validar els nostres resultats de laboratori a la clínica i aprofitar les biòpsies dels pacients per a estudis correlatius.
Figura: El càncer de pròstata letal té un paisatge molecular diferent del càncer de pròstata localitzat i curable. Un coneixement més gran del valor pronòstic i predictiu dels diferents biomarcadors genòmics en els diferents estats clínics de la malaltia pot ajudar a avançar en moltes de les necessitats clíniques no cobertes dels pacients amb càncer de pròstata, enumerades a la columna dreta de la figura. Adaptat de Mateu et al., Nature Cancer, 2020.
Cap de grup
Joaquin Mateo
Investigador sènior
Nicolas Herranz
Becària postdoctoral
Irene Casanova
Luisa Delgado
Becari Recerca Clínica
Pablo Cresta
Estudiants de doctorat
Sara Arce
Julian Brandariz
Tècniques
Laura Agundez
Teresa Casals
Sarai Cordoba
Lara de Llobet
Andrei Salca
Conservadora de dades clíniques
Magdalena Guardiola
Bioinformàtic
Daniel Aguilar
Estudiant de màster
Arnau Solé
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- Cresta Morgado P, Mateo J. Clinical implications of homologous recombination repair mutations in prostate cancer. Prostate. 2022 Aug;82 Suppl 1:S45-S59.
- Westphalen CB, Fine AD, André F, Ganesan S, Heinemann V, Rouleau E, Turnbull C, Garcia Palacios L, Lopez JA, Sokol ES, Mateo J. Pan-cancer Analysis of Homologous Recombination Repair-associated Gene Alterations and Genome-wide Loss-of-Heterozygosity Score. Clin Cancer Res. 2022 Apr 1;28(7):1412-1421.
- Mateo J, Steuten L, Aftimos P, André F, Davies M, Garralda E, Geissler J, Husereau D, Martinez-Lopez I, Normanno N, Reis-Filho JS, Stefani S, Thomas DM, Westphalen CB, Voest E. Delivering precision oncology to patients with cancer. Nat Med. 2022 Apr;28(4):658-665.
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- Neeb A, Herranz N, Arce-Gallego S, Miranda S, Buroni L, Yuan W, Athie A, Casals T, Carmichael J, Rodrigues DN, Gurel B, Rescigno P, Rekowski J, Welti J, Riisnaes R, Gil V, Ning J, Wagner V, Casanova-Salas I, Cordoba S, Castro N, Fenor de la Maza MD, Seed G, Chandran K, Ferreira A, Figueiredo I, Bertan C, Bianchini D, Aversa C, Paschalis A, Gonzalez M, Morales- Barrera R, Suarez C, Carles J, Swain A, Sharp A, Gil J, Serra V, Lord C, Carreira S, Mateo J, de Bono JS. Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors. Eur Urol. 2021 Feb;79(2):200-211.
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- Westphalen B, Fine AD, Andre F, Ganesan S, Heinemann V, Rouleau E, Turnbull C, Garcia Palacios L, Lopez JA, Sokol ES, Mateo J. Pan-cancer Analysis of Homologous Recombination Repair-associated Gene Alterations and Genome-wide Loss of Heterozygosity Score. Clin Cancer Res. 2021 Nov 5:clincanres.2096.2021. Epub ahead of print.
- Casanova-Salas I, Athie A, Boutros PC, Del Re M, Miyamoto DT, Pienta KJ, Posadas EM, Sowalsky AG, Stenzl A, Wyatt AW, Mateo J. Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer. Eur Urol. 2021 Jun;79(6):762-771. doi: 10.1016/j.eururo.2020.12.037. Epub 2021 Jan 7
- Rescigno P, Gurel B, Pereira R, Crespo M, Rekowski J, Rediti M, Barrero M, Mateo J, Bianchini D, Messina C, Fenor de la Maza MD, Chandran K, Carmichael J, Guo C, Paschalis A, Sharp A, Seed G, Figueiredo I, Lambros M, Miranda S, Ferreira A, Bertan C, Riisnaes R, Porta N, Yuan W, Carreira S, de Bono JS. Characterizing CDK12-Mutated Prostate Cancers. Clin Cancer Res. 2021 Jan 15;27(2):566-574. doi: 10.1158/1078-0432.CCR-20-2371. Epub 2020 Sep 28
- Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. doi: 10.1056/NEJMoa2022485. Epub 2020 Sep 20
- de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. doi: 10.1056/NEJMoa1911440. Epub 2020 Apr 28.PMID: 32343890
- Neeb A, Herranz N, Arce-Gallego S, Miranda S, Buroni L, Yuan W, Athie A, Casals T, Carmichael J, Rodrigues DN, Gurel B, Rescigno P, Rekowski J, Welti J, Riisnaes R, Gil V, Ning J, Wagner V, Casanova-Salas I, Cordoba S, Castro N, Fenor de la Maza MD, Seed G, Chandran K, Ferreira A, Figueiredo I, Bertan C, Bianchini D, Aversa C, Paschalis A, Gonzalez M, Morales- Barrera R, Suarez C, Carles J, Swain A, Sharp A, Gil J, Serra V, Lord C, Carreira S, Mateo J, de Bono JS. Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors. Eur Urol. 2021 Feb;79(2):200-211.
- Mateo J, Porta N, Bianchini D, McGovern U, Elliott T, Jones R, Syndikus I, Ralph C, Jain S, Varughese M, Parikh O, Crabb S, Robinson A, McLaren D, Birtle A, Tanguay J, Miranda S, Figueiredo I, Seed G, Bertan C, Flohr P, Ebbs B, Rescigno P, Fowler G, Ferreira A, Riisnaes R, Pereira R, Curcean A, Chandler R, Clarke M, Gurel B, Crespo M, Nava Rodrigues D, Sandhu S, Espinasse A, Chatfield P, Tunariu N, Yuan W, Hall E, Carreira S, de Bono JS. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jan;21(1):162-174.
- Mateo J, Cheng HH, Beltran H, DollingD, XuW, Pritchard CC, MossopH, RescignoP, Perez-LopezR, SailerV, Kolinsky M, BalasopoulouA, BertanC, NanusDM, TagawaST, ThorneH, MontgomeryB, CarreiraS, Shahneen Sandhu S, RubinMA, Nelson PS, de BonoClinical outcome of prostate cancer patients with germline DNA repair mutations: follow-up from an international study. Eur Orol. 2018 doi:10.1016/j.euro.2018.01.010
- Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard JY, Van Allen EM, Schultz N, Swanton C, André F, Pusztai L. A framework to rank genomic alterations as targets for cancer precision medicine: The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol.2018 Sep 1;29(9):1895-1902.
- Rodrigues DN, Rescigno P, Liu D, Yuan W, Carreira S, Lambros MB, Seed G, Mateo J, Riisnaes R, Mullane S, Margolis C, Miao D, Miranda S, Dolling D, Clarke M, Bertan C, Crespo M, Boysen G, Ferreira A, Sharp A, Figueiredo I, Keliher D, Aldubayan S, Burke KP, Sumanasuriya S, Fontes MS, Bianchini D, Zafeiriou Z, Mendes LST, Mouw K, Schweizer MT, Pritchard CC, Salipante S, Taplin ME, Beltran H, Rubin MA, Cieslik M, Robinson D, Heath E, Schultz N, Armenia J, Abida W, Scher H, Lord C, D’Andrea A, Sawyers CL, Chinnaiyan AM, Alimonti A, Nelson PS, Drake CG, Van Allen EM, de Bono JS. Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer. J Clin Invest. 2018 Nov 1;128(11):5185.
- Mateo J, Carles J. Towards a New Classification for Metastatic Prostate Cancer. Eur Urol. 2019 Mar;75(3):383-384. Epub 2018 Nov 19.
Joaquin Mateo, Gopinath Ganji , Charlotte Lemech , Howard A. Burris , Sae-Won Han , Karen Swales et al. A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2017 Oct 1;23(19):5981-5992. - Mateo J,* Carreira S*, Sandhu S*, Miranda S, Mossop H, Perez-Lopez R, et al DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. 2015. N Engl J Med 373(18):1697-1708.
- Goodall J*, Mateo J*, Yuan W, Mossop H, Porta N, Miranda S et al. Circulating Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. Cancer Discov. 2017 Sep;7(9):1006-1017
- Pritchard C*, Mateo J*, Walsh M*, de Sarkar N, Abida W, Beltran H, et al. Inherited DNA repair gene mutations in men with metastatic prostate cancer. N Engl J Med, 2016; 375(5)443-45.
- Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro R, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015;161(5):1215–28.
- Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, et al. DNA Repair in Prostate Cancer: Biology and Clinical Implications. European Urology. 2017 Mar;71(3):417-425.
- Seed, W. Yuan, J. Mateo, S. Carreira, C. Bertan, M. Lambros, G. Boysen, et al. Gene Copy Number Estimation From Targeted Next Generation Sequencing Of Prostate Cancer Biopsies: Analytic Validation and Clinical Qualification. Clinical Cancer Research, 2017 Oct 15;23(20):6070-6077
Totes les publicacions
- Zurita AJ, Graf RP, Villacampa G, Raskina K, Sokol E, Jin D, Antonarakis ES, Li G, Huang RSP, Casanova-Salas I, Vivancos A, Carles J, Ross JS, Schrock AB, Oxnard GR, Mateo J. Genomic Biomarkers and Genome-Wide Loss-of-Heterozygosity Scores in Metastatic Prostate Cancer Following Progression on Androgen-Targeting Therapies. JCO Precis Oncol . 2022 Jul;6:e2200195.
- Cresta Morgado P, Mateo J. Clinical implications of homologous recombination repair mutations in prostate cancer. Prostate . 2022 Aug;82 Suppl 1:S45-S59.
- Westphalen CB, Fine AD, André F, Ganesan S, Heinemann V, Rouleau E, Turnbull C, Garcia Palacios L, Lopez JA, Sokol ES, Mateo J. Pan-cancer Analysis of Homologous Recombination Repair-associated Gene Alterations and Genome-wide Loss-of-Heterozygosity Score. Clin Cancer Res . 2022 Apr 1;28(7):1412-1421.
- Mateo J, Steuten L, Aftimos P, André F, Davies M, Garralda E, Geissler J, Husereau D, Martinez-Lopez I, Normanno N, Reis-Filho JS, Stefani S, Thomas DM, Westphalen CB, Voest E. Delivering precision oncology to patients with cancer. Nat Med . 2022 Apr;28(4):658-665
- Hussain M, Corcoran C, Sibilla C, Fizazi K, Saad F, Shore N, Sandhu S, Mateo J, Olmos D, Mehra N, Kolinsky MP, Roubaud G, Özgüroǧlu M, Matsubara N, Gedye C, Choi YD, Padua C, Kohlmann A, Huisden R, Elvin JA, Kang J, Adelman CA, Allen A, Poehlein C, de Bono J. Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib). Clin Cancer Res . 2022 Apr 14;28(8):1518-1530.
- Gillessen S, Bossi A, Davis ID, de Bono J, Fizazi K, James ND, Mottet N, Shore N, Small E, Smith M, Sweeney C, Tombal B, Antonarakis ES, Aparicio AM, Armstrong AJ, Attard G, Beer TM, Beltran H, Bjartell A, Blanchard P, Briganti A, Bristow RG, Bulbul M, Caffo O, Castellano D, Castro E, Cheng HH, Chi KN, Chowdhury S, Clarke CS, Clarke N, Daugaard G, De Santis M, Duran I, Eeles R, Efstathiou E, Efstathiou J, Ngozi Ekeke O, Evans CP, Fanti S, Feng FY, Fonteyne V, Fossati N, Frydenberg M, George D, Gleave M, Gravis G, Halabi S, Heinrich D, Herrmann K, Higano C, Hofman MS, Horvath LG, Hussain M, Alicja Jereczek-Fossa B, Jones R, Kanesvaran R, Kellokumpu-Lehtinen PL, Khauli RB, Klotz L, Kramer G, Leibowitz R, Logothetis CJ, Mahal BA, Maluf F, Mateo J, Matheson D, Mehra N, Merseburger A, Morgans AK, Morris MJ, Mrabti H, Mukherji D, Murphy DG, Murthy V, Nguyen PL, Oh WK, Ost P, O’Sullivan JM, Padhani AR, Pezaro C, Poon DMC, Pritchard CC, Rabah DM, Rathkopf D, Reiter RE, Rubin MA, Ryan CJ, Saad F, Pablo Sade J, Sartor OA, Scher HI, Sharifi N, Skoneczna I, Soule H, Spratt DE, Srinivas S, Sternberg CN, Steuber T, Suzuki H, Sydes MR, Taplin ME, Tilki D, Türkeri L, Turco F, Uemura H, Uemura H, Ürün Y, Vale CL, van Oort I, Vapiwala N, Walz J, Yamoah K, Ye D, Yu EY, Zapatero A, Zilli T, Omlin A. Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022. Eur Urol . 2022 Dec 6:S0302-2838(22)02789-0.
- Mateo J, Beltran H. Moving Precision Oncology for Advanced Prostate Cancer from Theory to Practice. Eur Urol Focus . 2022 Aug 20:S2405-4569(22)00173-0.
- Mucci LA, Vinson J, Gold T, Gerke T, Filipenko J, Green RM, Anderson SG, Badal S, Bjartell A, Chi KN, Davis ID, Enting D, Fay AP, Lazarus J, Mateo J, McDermott R, Odedina FT, Olmos D, Omlin A, Popoola AA, Ragin C, Roberts R, Russnes KM, Waihenya C, Stopsack KH, Hyslop T, Villanti P, Kantoff PW, George DJ; IRONMAN Global Team. IRONMAN: A Novel International Registry of Men With Advanced Prostate Cancer. JCO Glob Oncol . 2022 Nov;8:e2200154.
- Graf RP, Fisher V, Mateo J, Gjoerup OV, Madison RW, Raskina K, Tukachinsky H, Creeden J, Cunningham R, Huang RSP, Mata DA, Ross JS, Oxnard GR, Venstrom JM, Zurita AJ. Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer. Eur Urol . 2022 Jan;81(1):37-47.
- Casanova-Salas I, Athie A, Boutros PC, Del Re M, Miyamoto DT, Pienta KJ, Posadas EM, Sowalsky AG, Stenzl A, Wyatt AW, Mateo J. Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer. Eur Urol. 2021 Jun;79(6):762-771.
- Neeb A, Herranz N, Arce-Gallego S, Miranda S, Buroni L, Yuan W, Athie A, Casals T, Carmichael J, Rodrigues DN, Gurel B, Rescigno P, Rekowski J, Welti J, Riisnaes R, Gil V, Ning J, Wagner V, Casanova-Salas I, Cordoba S, Castro N, Fenor de la Maza MD, Seed G, Chandran K, Ferreira A, Figueiredo I, Bertan C, Bianchini D, Aversa C, Paschalis A, Gonzalez M, Morales- Barrera R, Suarez C, Carles J, Swain A, Sharp A, Gil J, Serra V, Lord C, Carreira S, Mateo J, de Bono JS. Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors. Eur Urol. 2021 Feb;79(2):200-211.
- Carreira S, Porta N, Arce-Gallego S, Seed G, Llop-Guevara A, Bianchini D, Rescigno P, Paschalis A, Bertan C, Baker C, Goodall J, Miranda S, Riisnaes R, Figueiredo I, Ferreira A, Pereira R, Crespo M, Gurel B, Nava Rodrigues D, Pettitt SJ, Yuan W, Serra V, Rekowski J, Lord CJ, Hall E, Mateo J, de Bono JS. Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial. Cancer Discov. 2021 Nov;11(11):2812-2827.
- Westphalen B, Fine AD, Andre F, Ganesan S, Heinemann V, Rouleau E, Turnbull C, Garcia Palacios L, Lopez JA, Sokol ES, Mateo J. Pan-cancer Analysis of Homologous Recombination Repair-associated Gene Alterations and Genome-wide Loss of Heterozygosity Score. Clin Cancer Res. 2021 Nov 5:clincanres.2096.2021. Epub ahead of print.
- Mateo J, Seed G. Bertan C, Rescigno P, Dolling D, Figueiredo I, et al. (2019)Genomics of lethal prostate cancer at diagnosis and castration-resistance. J Clin Inv., ePub ahead of print, Dec.; DOI 10.1172/JCI132031.
- Mateo J, Porta N, Bianchini D, McGovern U, Elliot T, Jones R et al. (2019) Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncology, ePub ahead of print, Dec 2019; DOI: 10.1016/S1470-2045(19)30684-9.
- Athie A, Arce S, Gonzalez M, Morales R, Suarez C, Casals T, Hernandez G, Carles J, Mateo J. Targeting DNA Repair Defects for Precision Medicine in Prostate Cancer. Curr Onc Rep. 2019. 1007/s11912-019-0790-6
- Abida, Wassim; Cyrta, Joanna; Heller, Glenn; Prandi, Davide; Armenia, Joshua; Coleman, Ilsa; Cieslik, Marcin; Benelli, Matteo; Robinson, Dan; Van Allen, Eliezer M; Sboner, Andrea; Fedrizzi, Tarcisio; Mosquera, Juan Miguel; Robinson, Brian D; De Sarkar, Navonil; Kunju, Lakshmi P; Tomlins, Scott; Wu, Yi Mi; Nava Rodrigues, Daniel; Loda, Massimo; Gopalan, Anuradha; Reuter, Victor E; Pritchard, Colin C; MATEO, JOAQUIN; Bianchini, Diletta; Miranda, Susana; Carreira, Suzanne; Rescigno, Pasquale; Filipenko, Julie; Vinson, Jacob; Montgomery, Robert B; Beltran, Himisha; Heath, Elisabeth I; Scher, Howard I; Kantoff, Philip W; Taplin, Mary-Ellen; Schultz, Nikolaus; deBono, Johann S; Demichelis, Francesca; Nelson, Peter S; Rubin, Mark A; Chinnaiyan, Arul M; Sawyers, Charles L. Genomic correlates of clinical outcome in advanced prostate cancer. Proc Nat Acad Sci. 2019. 1073/pnas.1902651116
- Zafeiriou, Zafeiris; Bianchini, Diletta; Chandler, Robert; Rescigno, Pasquale; Yuan, Wei; Carreira, Suzanne; Barrero, Maialen; Petremolo, Antonella; Miranda, Susana; Riisnaes, Ruth; Rodrigues, Daniel Nava; Gurel, Bora; Sumanasuriya, Semini; Paschalis, Alec; Sharp, Adam; MATEO, JOAQUIN; Tunariu, Nina; Chinnaiyan, Arul M; Pritchard, Colin C; Kelly, Kevin; de Bono, Johann S. Genomic Analysis of Three Metastatic Prostate Cancer Patients with Exceptional Responses to Carboplatin Indicating Different Types of DNA Repair Deficiency. European Urology, 2019. 10.1016/j.eururo.2018.09.048
- Nava Rodrigues, Daniel; Casiraghi, Nicola; Romanel, Alessandro; Crespo, Mateus; Miranda, Susana; Rescigno, Pasquale; Figueiredo, Ines; Riisnaes, Ruth; Carreira, Suzanne; Sumanasuriya, Semini; Gasperini, Paola; Sharp, Adam; MATEO, JOAQUIN; Makay, Alan; McNair, Christopher; Schiewer, Matthew; Knudsen, Karen; Boysen, Gunther; Demichelis, Francesca; de Bono, Johann S. Clin Cancer Res, 2019. 10.1158/1078-0432.CCR-18-2068
- MATEO, JOAQUIN; Fizazi, Karim; Gillessen, Silke; Heidenreich, Axel; PEREZ LOPEZ, RAQUEL; Oyen, Wim J G; Shore, Neal; Smith, Matthew; Sweeney, Christopher; Tombal, Bertrand; Tomlins, Scott A; de Bono, Johann S. Managing Nonmetastatic Castration-resistant Prostate Cancer. European Urology, 2019. 10.1016/j.eururo.2018.07.035
- MATEO, JOAQUIN; Lord, C J; SERRA, VIOLETA; Tutt, A; BALMAÑA, JUDITH; CASTROVIEJO, CRISTINA; CRUZ, CRISTINA; OAKNIN, ANA; Kaye, S B; de Bono, J S. A decade of clinical development of PARP inhibitors in perspective. Ann Onc, 2019. 10.1093/annonc/mdz192
- Sharp, Adam; Welti, Jon C; Lambros, Maryou B K; Dolling, David; Rodrigues, Daniel Nava; Pope, Lorna; Aversa, Caterina; Figueiredo, Ines; Fraser, Jennifer; Ahmad, Zai; Lu, Changxue; Rescigno, Pasquale; Kolinsky, Michael; Bertan, Claudia; Seed, George; Riisnaes, Ruth; Miranda, Susana; Crespo, Mateus; Pereira, Rita; Ferreira, Ana; Fowler, Gemma; Ebbs, Berni; Flohr, Penny; Neeb, Antje; Bianchini, Diletta; Petremolo, Antonella; Sumanasuriya, Semini; Paschalis, Alec; MATEO, JOAQUIN; Tunariu, Nina; Yuan, Wei; Carreira, Suzanne; Plymate, Stephen R; Luo, Jun; de Bono, Johann S. Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer. European Urology. 10.1016/j.eururo.2019.04.006
- Mateo J, Cheng HH, Beltran H, Dolling D, Xu W, Pritchard C, et al. Clinical outcome of prostate cancer patients with germline DNA repair mutations: follow-up from an international study. Eur Urol. 2018 doi:10.1016/j.euro.2018.01.010
- Nava-Rodrigues D, Rescigno P, Liu D, Yuan W, Carreira S, Lambros M, et al. Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer, J Clin Inv. 2018; 128-11, pp.5185-5185.
- Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, et al. A framework to rank genomic alterations as targets for cancer precision medicine: The ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol., August 2018, 29-9: 1895-1902.
Boysen G, Nava Rodrigues D, Rescigno P, Seed G, Dolling DI, Riisnaes R, Crespo M, et al. SPOP mutated/ CHD1 deleted lethal prostate cancer and abiraterone sensitivity. Clin Can Res. 2018; 24-22: 5585-5593. - Mateo J, Carles J. 2018. Towards a New Classification for Metastatic Prostate Cancer, Eur Urol.
- Lorente, D, Olmos D, Mateo J et al. 2018. Circulating tumour cell increase as a biomarker of disease progression in metastatic castration-resistant prostate cancer patients with low baseline CTC counts. Ann Oncol. 29-7, pp.1554-1560.
- Joaquin Mateo , Gopinath Ganji , Charlotte Lemech , Howard A. Burris , Sae-Won Han , Karen Swales , Shaun Decordova , Maurice P DeYoung , Deborah A Smith , Shanker Kalyana-Sundaram , Jiuhua Wu , Monica Motwani , Rakesh Kumar , Jerry M Tolson , Sun Young Rha , Hyun Cheol Chung , Joseph Paul Eder , Sunil Sharma, Yung-Jue Bang , Jeffrey R. Infante ,Li Yan, Johann de Bono, Hendrik-Tobias Arkenau. A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2017 Oct 1;23(19):5981-5992.
- Seed G, Yuan W, Mateo J, Carreira S, Bertan C, Lambros M, Boysen G, Ferraldeschi R, Miranda S, Figueiredo I, Riisnaes R, Crespo M, Rodrigues DN, Talevich E, Robinson DR, Kunju LP, Wu YM, Lonigro R, Sandhu S, Chinnayan A, de Bono JS. Gene Copy Number Estimation from Targeted Next-Generation Sequencing of Prostate Cancer Biopsies: Analytic Validation and Clinical Qualification. Clin Cancer Res. 2017 Oct 15;23(20):6070-6077.
- Goodall J*, Mateo J*, Yuan W, Mossop H, Porta N, Miranda S, Perez-Lopez R, Dolling D, Robinson DR, Sandhu S, Fowler G, Ebbs B, Flohr P, Seed G, Nava Rodrigues D, Boysen G, Bertan C, Atkin M, Clarke M, Crespo M, Figueiredo I, Riisnaes R, Sumanasuriya S, Rescigno P, Zafeiriou Z, Sharp A, Tunariu N, Bianchini D, Gillman A, Lord CJ, Hall E, Chinnaiyan AM, Carreira S, de Bono JS. Circulating Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. Cancer Discovery. 2017 Apr 27 [Epub ahead of print] DOI: 10.1158/2159-8290.CD-17-0261
- Massard C, Mateo J, Loriot Y, Pezaro C, Albiges L, Mehra N, Varga A, Bianchini D, Ryan CJ, Petrylak DP, Attard G, Shen L, Fizazi K, de Bono J. : Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone. Annals of Oncology. 2017 Jan 1;28(1):90-95
- Pritchard C*, Mateo J*, Walsh M*, de Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin M, Robinson D, Lonigro R, Hussein M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, Aldubayan S, Han C, Beightol M, Morissey C, Nghiem B, Cheng H, Montgomery B, Walsh T, Casadei S, Vijai J, Scher H, Sawyers C, Schultz N, Kantoff P, Solit D, Robson M, Van Allen E, Offit K, de Bono JS, Nelson P. (on behalf of the SU2C-PCF Prostate Cancer Dream Team] Inherited DNA repair gene mutations in men with metastatic prostate cancer. N Engl J Med, 2016; 375(5)443-45.
- Mateo J,* Carreira S*, Sandhu S*, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A’Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. 2015. N Engl J Med 373(18):1697-1708.
- Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro R, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng F, Tomlins SA, Conney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, Reuter VE, Gopalan A, Gao J, Loda M, Lis RT, Bowden M, Balk SP, Gaviola G, Sougnez C, Gupta M, Yu, EY, Mostaghel EA, Cheng HH, Mulcahy H, True L, Plymate SR, Dyinge H, Ferraldeschi R, Flohr P, Miranda S, Zafeiriou Z, Tunariu N, Mateo J, Perez-Lopez R, Demichelis F, Robinson B, Schiffman M, Nanus DM, Tagawa ST, Sigaras A, Eng KW, Elemento O, Sboner A, Heath EI, Scher HI, Pienta KJ, Kantoff P, de Bono JS, Rubin MA, Nelson PA, Garraway LA, Sawyers CL, Chinnaiyan AM. Integrative clinical genomics of advanced prostate cancer. Cell 2015;161(5):1215–28.
- Perez-Lopez R, Mateo J, Mossop H, Blackledge MD, Collins DJ, Rata M, Morgan VA, Macdonald A, Sandhu S, Lorente D, Rescigno P, Zafeiriou Z, Bianchini D, Porta N, Hall E, Leach MO, de Bono JS, Koh DM, Tunariu N. Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study. Radiology. 2017 Apr;283(1):168-177
- Perez-Lopez R, Lorente D, Blackledge MD, Collins DJ, Mateo J, Bianchini D, Omlin A, Zivi A, Leach MO, de Bono JS, Koh DM, Tunariu N. Volume of Bone Metastasis Assessed with Whole-Body Diffusion-weighted Imaging Is Associated with Overall Survival in Metastatic Castration-resistant Prostate Cancer. Radiology 2016; 280(1):151-160.
- Ferraldeschi R, Nava D, Riisnaes R, Miranda S, Figueiredo I, Rescigno P, Ravi P, Pezaro C, Omlin A, Lorente D, Zafeiriou Z, Mateo J, Altavilla A, Sideris S, Bianchini D, Girst E, Thway K, Perez-Lopez R, Tunariu N, Parker C, Dearnaley D, Reid A, Attard G, de Bono JS. PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. European Urology 2015;67(4):795–802.
- Mateo J, Olmos D, Dumez H, Poondru S, Samberg N, Barr S, Van Tornout JM, Jie F, Sandhu S, Tan DS, Moreno V, LoRusso PM, Kaye SB, Schoffski P. A first-in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. Br J Cancer 2016, 114, 889-896
- Mateo J, Moreno V, Gupta A, Kaye SB, Dean E, Middleton MR, Friedlander M, Gourley C, Plummer R, Rustin G, Sessa C, Leunen K, Ledermann J, Swaisland H, Fielding A, Bannister W, Nicum S, Molife LR. An adaptive study to determine the optimal dose of the tablet formulation of the PARP inhibitor Olaparib. Target Oncol. 2016 Jun;11(3):401-15
- McDaniel AS, Ferraldeschi R, Krupa R, Landers M, Graf R, Louw J, Jendrisak A, Bales N, Marrinucci D, Zafeiriou Z, Flohr P, Sideris S, Crespo M, Figueiredo I, Mateo J, de Bono JS, Dittamore R, Tomlins SA, Attard G. Phenotypic diversity of circulating tumour cells in patients with metastatic castration-resistant prostate cancer. BJU Int. 2016 Aug (EPub)
- Rescigno P, Lorente D, Bianchini D, Ferraldeschi R, Kolinsky MP, Sideris S, Zafeiriou Z, Sumanasuriya S, Smith AD, Mehra N, Jayaram A, Perez-Lopez R, Mateo J, Parker C, Dearnaley DP, Tunariu N, Reid A, Attard G, de Bono JS. Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer. European Urology. 2016 Nov;70(5):724-731.
- Lorente D, Olmos D, Mateo J, Bianchini D, Seed G, Fleisher M, Danila DC, Flohr P, Crespo M, Figueiredo I, Miranda S, Baeten K, Molina A, Kheoh T, McCormack R, Terstappen LW, Scher HI, de Bono JS. Decline in Circulating Tumor Cell Count and Treatment Outcome in Advanced Prostate Cancer. European Urology. 2016; 70*6)985-992.
- Lorente D, Omlin A, Zafeiriou Z, Nava-Rodrigues D, Pérez-López R, Pezaro C, Mehra N, Sheridan E, Figueiredo I, Riisnaes R, Miranda S, Crespo M, Flohr P, Mateo J, Altavilla A, Ferraldeschi R, Bianchini D, Attard G, Tunariu N, de Bono J. Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses. Clin Genitourin Cancer. 2016 Dec;14(6):485-493
- Frenel J-S, Carreira S, Goodall J, Roda-Perez D, Perez-Lopez R, Tunariu N, Riisnaes R, Miranda S, Figueiredo I, Nava Rodrigues D, Smith A, Leux C, Garcia-Murillas I, Ferraldeschi R, Lorente D, Mateo J, Ong M, Yap TA, Banerji U, Gasi D, Turner N, Attard G, de Bono JS. Serial Next Generation Sequencing of Circulating Cell Free DNA Evaluating Tumour Clone Response To Molecularly Targeted Drug Administration. Clin Cancer Res 2015; 21(20):4586-96.
- Lorente D, Mateo J, Templeton AJ, Zafeiriou Z, Bianchini D, Ferraldeschi R, Bahl A, Shen L, Su Z, Sartor O, de Bono JS. Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use. Ann Oncol. 2015 Apr;26(4):750-5
- Ferraldeschi R, Nava Rodrigues D, Riisnaes R, Miranda S, Figueiredo I, Rescigno P, Ravi P, Pezaro C, Omlin A, Lorente D, Zafeiriou Z, Mateo J, Altavilla A, Sideris S, Bianchini D, Grist E, Thway K, Perez Lopez R, Tunariu N, Parker C, Dearnaley D, Reid A, Attard G, de Bono J. PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol. 2015 Apr;67(4):795-802
- Wilbaux M, Tod M, De Bono J, Lorente D, Mateo J, Freyer G, You B, Hénin E. A Joint Model for the Kinetics of CTC Count and PSA Concentration During Treatment in Metastatic Castration-Resistant Prostate Cancer. CPT Pharmacometrics Syst Pharmacol. 2015 May;4(5):277-85
- Mateo J, Berlin J, de Bono JS, Cohen RB, Keedy V, Mugundu G, Zhang L, Abbattista A, Davis C, Gallo Stampino C, Borghaei H. A first-in-human study of the anti-α5β1 integrin monoclonal antibody PF-04605412 administered intravenously to patients with advanced solid tumors. Cancer Chemother Pharmacol 2014, 74(5):1039-46.
- Ong M, Carreira S, Goodall J, Mateo J, Figueiredo I, Rodrigues DN, Perkins G, Seed G, Yap TA, Attard G, de Bono JS. Validation and utilisation of high-coverage next-generation sequencing to deliver the pharmacological audit trail. Br J Cancer 2014;111(5):828-36.
- Ravi P, Mateo J, Lorente D, Zafeiriou Z, Altavilla A, Ferraldeschi R, Sideris S, Grist E, Smith A, Wong S, Bianchinni D, Attard G, de Bono JS. External Validation of a Prognostic Model Predicting Overall Survival in Metastatic Castrate-resistant Prostate Cancer Patients Treated with Abiraterone. European Urology 2014;66(1):8–11.
- Barber LJ, Sandhu S, Chen L, Campbell J, Kozarewa I, Fenwick K, Assiotis I, Rodrigues DN, Reis Filho JS, Moreno V, Mateo J, Molife LR, De Bono J, Kaye S, Lord CJ, Ashworth A. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J Pathol. 2013 Feb;229(3):422-9.
- Mateo J, Carreira S, de Bono JS. Acquiring evidence for precision prostate cancer care. Annals Oncology. 2017 Apr 13. (Epub ahead of print)
- Mateo J, Sharp A, de Bono JS. Investigating Genomic Aberrations of the Androgen Receptor: Moving Closer to More Precise Prostate Cancer Care? European Urology. 2017 Feb 20.
- Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, Olmos D, Pritchard CC, Rubin MA, de Bono JS. DNA Repair in Prostate Cancer: Biology and Clinical Implications. European Urology. 2017 Mar;71(3):417-425.
- Lorente D, Mateo J, Perez-Lopez R, de Bono JS, Attard G. Sequencing agents in metastatic prostate cancer. Lancet Oncology 2015 Jun;16(6):e279-92.
- Lorente D, Mateo J, Zafeiriou Z, Smith AD, Sandhu S, Ferraldeschi R, de Bono JS. Switching and withdrawing hormonal agents for castration-resistant prostate cancer. Nat Rev Urol. 2015 Jan;12(1):37-47.
- Mateo J, Gerlinger M, Rodrigues DN, de Bono JS. The promise of circulating tumor cell analysis in cancer management Genome Biol. 2014 Aug 30;15(8):448.
- Mateo J, Ong M, Tan DS, Gonzalez MA, de Bono JS. Appraising iniparib, the PARP inhibitor that never was–what must we learn? Nat Rev Clin Oncol. 2013 Dec;10(12):688-696.
- Clinical Qualification of DNA Repair Defects as Biomarkers in Metastatic Prostate Cancer Using Integrated Genomics and Tissue-Based Functional Assays.
Grantor: US Department of Defense Congressionally-Directed Medical Research Program. - Co-targeting androgen receptor signalling and DNA damage repair for precision therapy in advanced prostate.
Grantor: European Commission H2020 Program. - Novel approaches to liquid biopsy in prostate cancer to inform precision medicine.
Grantor: FERO Foundation. - Leveraging the AR-DDR interaction in de-novo metastatic prostate cancer towards precision combination therapies with PARP inhibitors.
Grantor: AECC (Fundación Asociación Española contra el Cáncer). - Integrated analysis of blood circulating tumor signatures to monitor genomic evolution and therapy responses in advanced Prostate Cancer.
Grantor: ”la Caixa” - Exploiting senescence in a two-step approach to treat advanced Prostate Cancer.
Grantor: Instituto de Salud Carlos III (ISCIII). - Tumoral senescence induced by anti-cancer therapies constitutes a novel prognostic biomarker and a therapeutic target.
Grantor: AECC (Fundación Asociación Española contra el Cáncer). - Prostate Cancer Genomic Evolution and Signatures of DNA Damage Repair Deficiencies.
Grantor: CRIS Cancer Foundation. - Title: Development of NT1, a potent and selective best-in-class drug targeting the Androgen Receptor disordered domain for the treatment of Castration Resistant Prostate Cancer . Grantor: Agencia Estatal de Investigación – Ministerio de Ciencia e Innovación. Ref: CPP2022-009651. Duration: 01/10/2023 – 30/09/2026. Coordinator: Nuage Therapeutics, S.L.. Other Partners: Fundació Institut de Recerca Biomédica (Barcelona). PI VHIO: Joaquín Mateo.
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