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.
Tot i aquests avenços per tal de gestionar de manera més eficaç el CPRCm, continua sent una malaltia letal amb una taxa de morbiditat i mortalitat important arreu del món. Es pot dir que la necessitat més urgent a l’hora de desenvolupar fàrmacs contra el CPRC és l’estratificació molecular del tractament. En paral·lel, cal continuar centrant els esforços en la identificació de biomarcadors predictius de la resposta sòlids i en el desenvolupament de teràpies anticanceroses dirigides. L’arribada d’aquests tractaments nous ha dut l’evolució dels tumors cap a un canvi en el panorama genòmic que s’observa en els pacients amb la malaltia avançada.
Quant a la recerca, adoptem un enfocament exhaustiu i integral. D’aquesta manera, el nostre grup engloba la biologia molecular, la genòmica dels tumors, els assajos clínics i la ciència computacional per tal de desenvolupar estratègies mèdiques de precisió a l’hora de tractar el càncer de pròstata avançat a partir de biomarcadors predictius de la resposta.
S’observen defectes en els gens de reparació del dany a l’ADN (DDR són les sigles en anglès) —en especial en els trencaments de cadena doble— en el 20-25 % dels casos de CPRCm, i ens permeten estudiar com podem oferir un tractament i unes cures contra el càncer més precisos. Algunes d’aquestes mutacions tenen implicacions pronòstiques i predictives que són crucials a l’hora de complir la promesa d’una medicina personalitzada en el camp de l’oncologia. Hem publicat els resultats finals de l’assaig per al registre d’olaparib, que és un inhibidor de PARP, en el càncer de pròstata, fet que en propicia l’autorització a Europa, el Canadà i els Estats Units, entre altres països. De tota manera, cal treballar més per atènyer una oferta adequada de tractaments amb inhibidors de PARP per a aquells pacients amb mutacions del gen DDR més enllà del BRCA2.
L’interès per la modulació del cicle cel·lular a partir del dany a l’ADN també ens ha dut a estudiar el fenotip senescent observat després de l’exposició a fàrmacs dirigits, que, segons suposem, és un mecanisme de resistència farmacològica, i com el podem abordar des del punt de vista terapèutic. Amb l’objectiu de traduir aquestes conclusions en beneficis per als pacients com més aviat millor, estudiem les mateixes signatures genòmiques i transcriptòmiques en les biòpsies de pacients amb càncer de pròstata metastàtic. En paral·lel, recollim biòpsies líquides longitudinals per estudiar com evoluciona un tumor durant la resposta i progressió als fàrmacs dirigits. La nostra recerca se centra en estratègies d’estratificació del pacient òptimes per a l’assistència clínica, posant més èmfasi en la combinació de fàrmacs dirigits a la reparació de l’ADN amb aquells que inhibeixen la senyalització androgènica. I encara més important, hem posat en marxa uns primers assajos clínics iniciats per l’investigador, fet que tradueix els estudis de recerca al laboratori en intervencions terapèutiques per als pacients.
- Establir una reclassificació clínicament rellevant del càncer de pròstata metastàtic que integri dades genotípiques i fenotípiques amb assajos funcionals.
- Desenvolupar assajos d’estratificació molecular del càncer de pròstata basats en teixit tumoral i biomarcadors circulants.
- Optimitzar la combinació de fàrmacs dirigits a la reparació de l’ADN amb inhibidors del receptor androgènic.
- Construir un nucli de medicina de precisió per als pacients amb càncer de pròstata que es tracten a l’Hospital Universitari Vall d’Hebron (HUVH).
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
Estudiants de doctorat
Sara Arce
Julian Brandariz
Tècniques
Olaia Baylo
Teresa Casals
Sarai Cordoba
Lucila Gonzalez
Natalia Castro
Conservadora de dades clíniques
Magdalena Guardiola
Bioinformàtic
Daniel Aguilar
Estudiant de màster
Arnau Solé
Publicacions científiques més rellevants
- 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.
- 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
- 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.
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