Prostate Cancer Clinical Research Unit

David Olmos Head of Clinical Research Unit
T +34 (+34) 917 328 000 (Ext 2950)
dolmos@cnio.es

Staff Scientists

Pedro P. Lopez-Casas

Clinical Investigator

Daniel Alameda
Elena Castro

Post-Doctoral Fellows

Carlo Cattrini
Ylenia Cendón
David Martínez

Technicians

Eva María Casas
Federica Ferrante
Olga Popova
Leticia Rivera

Prostate cancer (PrCa) is one of the most heritable human cancers. Inherited mutations in several genes involved in DNA damage response and repair have been reported to predispose men to PrCa, including mutations in BRCA2. Seminal work from our Group has established that these mutations are an independent prognostic factor for the disease.

The Prostate Cancer Clinical Research Unit remains a major contributor to CNIO’s scientific productivity, with a total IF > 90 in 2019, and an accumulated IF > 500 since the Unit’s creation in 2012. These figures include 15 manuscripts led or co-led by the team in first-decile journals, and 3 major contributions to clinical practice included in the NCCN, EAU, ASCO, and/or ESMO PrCa management and treatment guidelines. Our associated CNIO-IBIMA CRU has consolidated as the biggest disease-specific CNIO clinical unit in numbers of CNIO sponsored studies and patients enrolled in these studies. The Unit has contributed significantly to major clinical trials in the field, such as SPARTAN or PROFOUND (both published in NEJM with D. Olmos as author), that led to the approvals of the novel anti-androgen apalutamide and the PARP inhibitor olaparib, respectively. In 2019, this Unit enrolled a record of 132 patients in prostate cancer trials.

Our Group continues to be successful in securing competitive national and international grants. 2019 was a record year in terms of funding: we received the ‘Excellence in Research’ CRIS Foundation Grant, the prestigious ‘Proyectos AECC Grant’, as well as 1 of the Top 3 AES-ISCIII research grants (both in scoring and financial support). Overall this positions our Unit as one of top performing units at CNIO, contributing significantly to the excellence profile of the institution.

Publications

Sweeney C, Bracarda S, Sternberg CN, Chi KN, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Parnis F, Atduev V, Buchschacher GL Jr, Gafanov R, Corrales L, Borre M, Stroyakovskiy D, Alves GV, Bournakis E, Puente J, Harle-Yge ML, Gallo J, Chen G, Hanover J, Wongchenko MJ, Garcia J, de Bono JS. (2021). Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet 398, 131-142. CNIO Publication.
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ (2021). Apalutamide and Overall Survival in Prostate Cancer. Eur Urol 79, 150-158. CNIO Publication.
Lozano R, Castro E, Aragón IM, Cendón Y, Cattrini C, López-Casas PP, Olmos D (2020). Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer. Br J Cancer 124, 552-563. CNIO Publication.
Khalaf DJ, Aragón IM, Annala M, Lozano R, Taavitsainen S, Lorente D, Finch DL, Romero-Laorden N, Vergidis J, Cendón Y, Oja C, Pacheco MI, Zulfiqar M; PROREPAIR-B investigators, Gleave ME, Wyatt AW, Olmos D, Chi KN, Castro E (2020). HSD3B1 (1245A>C) Germline Variant and Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer Patients Treated With Abiraterone and Enzalutamide: Results From Two Prospective Studies. Ann Oncol 31, 1186-1197. CNIO Publication.
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, Özgüroglu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators (2020). Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. New Engl J Med 383, 2345-2357. CNIO Publication.
Lorente D, Castro E, Lozano R, Puente J, Romero-Laorden N, Rodríguez-Vida A, Lainez N, Villatoro R, Llácer C, Cattrini C, Hernández A, Domenech M, Zambrana F, Almagro E, Luque R, Martinez E, López-Campos F, Gonzalez B, Méndez-Vidal MJ, Medina A, Piulats JM, Olmos D; PROREPAIR-B Study Investigators. (2020). Association Between Second Progression-free Survival (PFS2) and Overall Survival in Metastatic Castration-resistant Prostate Cancer. Eur Urol 77, 763-766. CNIO Publication.
Perez-Ruixo C, Ackaert O, Ouellet D, Chien C, Uemura H, Olmos D, Mainwaring P, Lee JY, Yu MK, Perez-Ruixo JJ, Smith MR, Small EJ (2020). Efficacy and Safety Exposure-Response Relationships of Apalutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer.. Clin Cancer Res 26, 4460-4467. CNIO Publication.
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. (2020). Olaparib for Metastatic Castration-Resistant Prostate Cancer.. New Engl J Med 382, 2091-2102. CNIO Publication.
Rescigno P, Dolling D, Conteduca V, Rediti M, Bianchini D, Lolli C, Ong M, Li H, Omlin AG, Schmid S, Caffo O, Zivi A, Pezaro CJ, Morley C, Olmos D, Romero-Laorden N, Castro E, Saez MI, Mehra N, Smeenk S, Sideris S, Gil T, Banks P, Sandhu SK, Sternberg CN, De Giorgi U, De Bono JS. (2020). Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis.. Eur Urol Oncol 3, 176-182. CNIO Publication.
Messina C, Cattrini C, Soldato D, Vallome G, Caffo O, Castro E, Olmos D, Boccardo F, Zanardi E (2020). BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications. Journal of Oncology 0, 4986365. CNIO Publication.
Cattrini C, Soldato D, Rubagotti A, Zinoli L, Zanardi E, Barboro P, Messina C, Castro E, Olmos D, Boccardo F (2020). Epidemiological Characteristics and Survival in Patients with De Novo Metastatic Prostate Cancer. Cancers 12, 2855. CNIO Publication.
Correa R , Navarro M , Lobato M , Otero A , Jerez I , Rico JM , Zapata I , Lupiañez Y , Medina JA, Olmos D, Gómez-Millán J (2020). Influence of the Technique and Comorbidities in Hypofractionated Radiotherapy for Prostate Cancer. Clin Transl Oncol 22, 311-318. CNIO Publication.
Oliva L, Lozano R, Llácer C, Aragón I, Pajares BI, Sáez MI, Herrera-Imbroda B, Montesa A, Hernández D, Villatoro R, Otero A, Correa R, Grau G, Peinado P, Pacheco MI, García-Galisteo E, Rueda A, Machuca FJ, Alba E, Márquez-Aragonés A, Olmos D, Castro E (2019). Risk Prediction Tools Available for Germline BRCA1/2 Mutations Underperform in Prostate Cancer Patients.. Eur Urol Oncol (in press). CNIO Publication.
Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR (2019). Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol 30, 1813-1820. CNIO Publication.
Cattrini C, Castro E, Lozano R, Zanardi E, Rubagotti A, Boccardo F, Olmos D (2019). Current Treatment Options for Metastatic Hormone-Sensitive Prostate Cancer. Cancers 11, E1355. CNIO Publication. Open Access
Lozano R, Almagro E, Castro E (2019). Relevance of radium-223 in hospital clinical practice from a medical oncologist point of view. Rev Esp Med Nucl Imagen Mol. 38, 106-111. CNIO Publication.
Conteduca V, Jayaram A, Romero-Laorden N, Wetterskog D, Salvi S, Gurioli G, Scarpi E, Castro E, Marin-Aguilera M, Lolli C, Schepisi G, Maugeri A, Wingate A, Farolfi A, Casadio V, Medina A, Puente J, Vidal MJM, Morales-Barrera R, Villa-Guzmán JC, Hernando S, Rodriguez-Vida A, González-Del-Alba A, Mellado B, Gonzalez-Billalabeitia E, Olmos D, Attard G, De Giorgi U (2019). Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer. Eur Urol 75, 368-373. CNIO Publication.
Naldaiz-Gastesi N, Goicoechea M, Aragón IM, Pérez-López V, Fuertes-Alvarez S, Herrera-Imbroda B, López de Munain A, de Luna-Diaz R, Baptista PM, Fernández MA, Lara MF, Izeta A (2019). Isolation and characterization of myogenic precursor cells from human cremaster muscle. Sci. Reports 9, 3454. CNIO Publication. Open Access
Nombela P, Lozano R, Aytes A, Mateo J, Olmos D, Castro E (2019). BRCA2 and Other DDR Genes in Prostate Cancer. Cancers 11, E352. CNIO Publication. Open Access
Castro E, Romero-Laorden N, Del Pozo A, Lozano R, Medina A, Puente J, Piulats JM, Lorente D, Saez MI, Morales-Barrera R, Gonzalez-Billalabeitia E, Cendón Y, García-Carbonero I, Borrega P, Mendez Vidal MJ, Montesa A, Nombela P, Fernández-Parra E, Gonzalez Del Alba A, Villa-Guzmán JC, Ibáñez K, Rodriguez-Vida A, Magraner-Pardo L, Perez-Valderrama B, Vallespín E, Gallardo E, Vazquez S, Pritchard CC, Lapunzina P, Olmos D (2019). PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol 37, 490-503. CNIO Publication.
Lorente D, Olmos D, Mateo J, Dolling D, Bianchini D, Seed G, Flohr P, Crespo M, Figueiredo I, Miranda S, Scher HI, Terstappen LWMM, de Bono JS. (2018). Circulating Tumor Cell Increase as a Biomarker of Disease Progression in Metastatic Castration-Resistant Prostate Cancer Patients with Low Baseline CTC Counts.. Ann Oncol (in press). CNIO Publication.
Lorente D, Olmos D, Mateo J, Dolling D, Bianchini D, Seed G, Flohr P, Crespo M, Figueiredo I, Miranda S, Scher HI, Terstappen LWMM, de Bono JS (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, 1554-1560. CNIO Publication.
Romero-Laorden N, Lozano R, Jayaram A, López-Campos F, Saez MI, Montesa A, Gutierrez-Pecharoman A, Villatoro R, Herrera B, Correa R, Rosero A, Pacheco MI, Garcés T, Cendón Y, Nombela MP, Van de Poll F, Grau G, Rivera L, López PP, Cruz JJ, Lorente D, Attard G, Castro E, Olmos D (2018). Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study). Br J Cancer 119, 1052-1059. CNIO Publication.
Rodriguez-Vida A, Torregrosa MD, Pinto Á, Climent MÁ, Olmos D, Carles J (2018). Selection and monitoring of patients with metastatic castration-resistant prostate cancer for treatment with radium-223. Clin Transl Oncol 20, 676-686. CNIO Publication.
Cassinello J, Arranz JÁ, Piulats JM, Sánchez A, Pérez-Valderrama B, Mellado B, Climent MÁ, Olmos D, Carles J, Lázaro M (2018). SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017). Clin Transl Oncol 20, 57-68. CNIO Publication.
Lawrence MG, Obinata D, Sandhu S, Selth LA, Wong SQ, Porter LH, Lister N, Pook D, Pezaro CJ, Goode DL, Rebello RJ, Clark AK, Papargiris M, Van Gramberg J, Hanson AR, Banks P, Wang H, Niranjan B, Keerthikumar S, Hedwards S, Huglo A, Yang R, Henzler C, Li Y, Lopez-Campos F, Castro E, Toivanen R, Azad A, Bolton D, Goad J, Grummet J, Harewood L, Kourambas J, Lawrentschuk N, Moon D, Murphy DG, Sengupta S, Snow R, Thorne H, Mitchell C, Pedersen J, Clouston D, Norden S, Ryan A, Dehm SM, Tilley WD, Pearson RB, Hannan RD, Frydenberg M, Furic L, Taylor RA, Risbridger GP (2018). Patient-derived models of abiraterone and enzalutamide resistant prostate cancer reveal sensitivity to ribosome-directed therapy. Eur Urol 74, 562-572. CNIO Publication.
Mikropoulos C, Selkirk CGH, Saya S, Bancroft E, Vertosick E, Dadaev T, Brendler C, Page E, Dias A, Evans DG, Rothwell J, Maehle L, Axcrona K, Richardson K, Eccles D, Jensen T, Osther PJ, van Asperen CJ, Vasen H, Kiemeney LA, Ringelberg J, Cybulski C, Wokolorczyk D, Hart R, Glover W, Lam J, Taylor L, Salinas M, Feliubadaló L, Oldenburg R, Cremers R, Verhaegh G, van Zelst-Stams WA, Oosterwijk JC, Cook J, Rosario DJ, Buys SS, Conner T, Domchek S, Powers J, Ausems MG, Teixeira MR, Maia S, Izatt L, Schmutzler R, Rhiem K, Foulkes WD, Boshari T, Davidson R, Ruijs M, Helderman-van den Enden AT, Andrews L, Walker L, Snape K, Henderson A, Jobson I, Lindeman GJ, Liljegren A, Harris M, Adank MA, Kirk J, Taylor A, Susman R, Chen-Shtoyerman R, Pachter N, Spigelman A, Side L, Zgajnar J, Mora J, Brewer C, Gadea N, Brady AF, Gallagher D, van Os T, Donaldson A, Stefansdottir V, Barwell J, James PA, Murphy D, Friedman E, Nicolai N, Greenhalgh L, Obeid E, Murthy V, Copakova L, McGrath J, Teo SH, Strom S, Kast K, Leongamornlert DA, Chamberlain A, Pope J, Newlin AC, Aaronson N, Ardern-Jones A, Bangma C, Castro E, Dearnaley D, Eyfjord J, Falconer A, Foster CS, Gronberg H, Hamdy FC, Johannsson O, Khoo V, Lubinski J, Grindedal EM, McKinley J, Shackleton K, Mitra AV, Moynihan C, Rennert G, Suri M, Tricker K; IMPACT study collaborators, Moss S, Kote-Jarai Z, Vickers A, Lilja H, Helfand BT, Eeles RA (2018). Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition. Br J Cancer 118, 266-276. CNIO Publication.
Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators (2018). Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. New Engl J Med 378, 1408-1418. CNIO Publication.
Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, Olmos D, Pritchard CC, Rubin MA, de Bono JS (2017). DNA Repair in Prostate Cancer: Biology and Clinical Implications.. Eur Urol 71, 417-425. CNIO Publication.
Banerjee S, Califano R, Corral J, de Azambuja E, De Mattos-Arruda L, Guarneri V, Hutka M, Jordan K, Martinelli E, Mountzios G, Ozturk MA, Petrova M, Postel-Vinay S, Preusser M, Qvortrup C, Volkov MNM, Tabernero J, Olmos D, Strijbos MH (2017). Professional Burnout in European Young Oncologists: Results of The European Society For Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.. Ann Oncol 28, 1590-1596. CNIO Publication.
García JL, Lozano R, Misiewicz-Krzeminska I, Fernández-Mateos J, Krzeminski P, Alfonso S, Marcos RA, García R, Gómez-Veiga F, Virseda Á, Herrero M, Olmos D, Cruz-Hernández JJ. (2017). A novel capillary nano-immunoassay for assessing androgen receptor splice variant 7 in plasma. Correlation with CD133 antigen expression in circulating tumor cells. A pilot study in prostate cancer patients.. Clin Transl Oncol 19, 1350-1357. CNIO Publication.
Moynihan C, Bancroft EK, Mitra A, Ardern-Jones A, Castro E, Page EC, Eeles RA (2017). Ambiguity in a masculine world: Being a BRCA1/2 mutation carrier and a man with prostate cancer.. Psycho-Oncol 26, 1987-1993. CNIO Publication.
Heinrich D, Bektic J, Bergman AM, Caffo O, Cathomas R, Chi KN, Daugaard G, Keizman D, Kindblom J, Kramer G, Olmos D, Omlin A, Sridhar SS, Tucci M, van Oort I, Nilsson S (2017). The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer. Clin Genitourin Cancer (in press). CNIO Publication.
Romero-Laorden N, Castro E (2017). Inherited mutations in DNA repair genes and cancer risk.. Curr Prob Cancer 41, 251-264. CNIO Publication.
Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, Fernandez-Ruiz S, Sutherland JD, Clasquin M, Tomas-Cortazar J, Jimenez J, Torres I, Quang P, Ximenez-Embun P, Bago R, Ugalde-Olano A, Loizaga-Iriarte A, Lacasa-Viscasillas I, Unda M, Torrano V, Cabrera D, van Liempd SM, Cendon Y, Castro E, Murray S, Revandkar A, Alimonti A, Zhang Y, Barnett A, Lein G, Pirman D, Cortazar AR, Arreal L, Prudkin L, Astobiza I, Valcarcel-Jimenez L, Zuñiga-García P, Fernandez-Dominguez I, Piva M, Caro-Maldonado A, Sánchez-Mosquera P, Castillo-Martín M, Serra V, Beraza N, Gentilella A, Thomas G, Azkargorta M, Elortza F, Farràs R, Olmos D, Efeyan A, Anguita J, Muñoz J, Falcón-Pérez JM, Barrio R, Macarulla T, Mato JM, Martinez-Chantar ML, Cordon-Cardo C, Aransay AM, Marks K, Baselga J, Tabernero J, Nuciforo P, Manning BD, Marjon K, Carracedo A (2017). mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.. Nature 547, 109-113. CNIO Publication.
Romero-Laorden N, Piñeiro-Yañez E, Gutierrez-Pecharroman A, Pacheco MI, Calvo E, Al-Shahrour F, Castro E, Olmos D (2017). Somatic BRCA2 bi-allelic loss in the primary prostate cancer was associated to objective response to PARPi in a sporadic CRPC patient.. Ann Oncol 28, 1158-1159. CNIO Publication.
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 (2016). Decline in Circulating Tumor Cell Count and Treatment Outcome in Advanced Prostate Cancer.. Eur Urol 70, 985-992. CNIO Publication.
Missiaglia E, Shepherd CJ, Aladowicz E, Olmos D, Selfe J, Pierron G, Delattre O, Walters Z, Shipley J (2016). MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.. Cancer Lett (in press). CNIO Publication.
Mateo J, Olmos D, Dumez H, Poondru S, Samberg NL, Barr S, Van Tornout JM, Jie F, Sandhu S, Tan DS, Moreno V, LoRusso PM, Kaye SB, Schöffski P. (2016). A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies.. Br J Cancer 114, 889-896. CNIO Publication.
Castro E, Mikropoulos C, Bancroft EK, Dadaev T, Goh C, Taylor N, Saunders E, Borley N, Keating D, Page EC, Saya S, Hazell S, Livni N, deSouza N, Neal D, Hamdy FC, Kumar P, Antoniou AC, Kote-Jarai Z; PROFILE Study Steering Committee, Eeles RA (2016). The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.. Oncologist 21, 716-722. CNIO Publication.
Castro E, Mateo J, Olmos D, de Bono JS (2016). Targeting DNA Repair: The Role of PARP Inhibition in the Treatment of Castration-Resistant Prostate Cancer.. Cancer J 22, 353-356. CNIO Publication.
Selfe J, Olmos D, Al-Saadi R, Thway K, Chisholm J, Kelsey A, Shipley J (2016). Impact of fusion gene status versus histology on risk-stratification for rhabdomyosarcoma: Retrospective analyses of patients on UK trials.. Pediatr Blood Cancer (in press). CNIO Publication.