“Este contenido se encuentra unicamente en inglés”

David Olmos Jefe de Grupo
T +34 917 328 000 (Ext 2950)
dolmos@cnio.es

Prostate cancer (PrCa) is one of the most heritable human cancers, as almost 60% of the PrCa risk is attributable to genetic factors. Inherited mutations in several genes involved in DNA damage response and repair (DDR) have been reported to predispose men to prostate cancer; this includes mutations in BRCA2, the genetic event known to confer the greatest risk of the disease. Recent studies have revealed that germline deleterious mutations in DDR genes are present in 8-12% of patients with metastatic PrCa, mutations in BRCA2 being the most prevalent ones. Our Group has previously established that these mutations are an independent prognostic factor for the disease. These observations have come full-circle with the development of Poly (ADP-ribose) polymerase inhibitors to treat advanced prostate cancer. Due to the high prevalence of DDR germline mutations and the implications for the patients and their families, clinical guidelines have recently been updated to recommend genetic screening to all patients with metastatic PrCa. In consequence, the number of mutation carriers is likely to grow over the next few years, whilst the most appropriate treatment and management still remains unknown. This year our Unit’s research has focussed on gaining a better understanding of the clinical implications of BRCA2 and other DDR defects ; the molecular characterisation of these tumours and the identification of biomarkers can enable us to predict the benefit derived from currently available therapies.

Publicaciones

• 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.(2019)
  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
  J Clin Oncol (in press).
• Circulating Tumor Cell Increase as a Biomarker of Disease Progression in Metastatic Castration-Resistant Prostate Cancer Patients with Low Baseline CTC Counts.(2018)
  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.
  Ann Oncol (in press).
• Circulating tumour cell increase as a biomarker of disease progression in metastatic castration-resistant prostate cancer patients with low baseline CTC counts.(2018)
  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.
  Ann Oncol 29, 1554-1560.
• 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).(2018)
  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
  Br J Cancer 119, 1052-1059.
• Selection and monitoring of patients with metastatic castration-resistant prostate cancer for treatment with radium-223.(2018)
  Rodriguez-Vida A, Torregrosa MD, Pinto Á, Climent MÁ, Olmos D, Carles J.
  Clin Transl Oncol 20, 676-686.
• SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017).(2018)
  Cassinello J, Arranz JÁ, Piulats JM, Sánchez A, Pérez-Valderrama B, Mellado B, Climent MÁ, Olmos D, Carles J, Lázaro M.
  Clin Transl Oncol 20, 57-68.
• Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer(2018)
  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.
  New Engl J Med 378, 1408-1418.
• mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.(2017)
  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
  Nature 547, 109-113.
• Somatic BRCA2 bi-allelic loss in the primary prostate cancer was associated to objective response to PARPi in a sporadic CRPC patient.(2017)
  Romero-Laorden N, Piñeiro-Yañez E, Gutierrez-Pecharroman A, Pacheco MI, Calvo E, Al-Shahrour F, Castro E, Olmos D
  Ann Oncol 28, 1158-1159.
• DNA Repair in Prostate Cancer: Biology and Clinical Implications.(2017)
  Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, Olmos D, Pritchard CC, Rubin MA, de Bono JS
  Eur Urol 71, 417-425.
• Professional Burnout in European Young Oncologists: Results of The European Society For Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.(2017)
  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
  Ann Oncol 28, 1590-1596.
• 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.(2017)
  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.
  Clin Transl Oncol 19, 1350-1357.
• Ambiguity in a masculine world: Being a BRCA1/2 mutation carrier and a man with prostate cancer.(2017)
  Moynihan C, Bancroft EK, Mitra A, Ardern-Jones A, Castro E, Page EC, Eeles RA
  Psycho-Oncol 26, 1987-1993.
• The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer.(2017)
  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
  Clin Genitourin Cancer (in press).
• Inherited mutations in DNA repair genes and cancer risk.(2017)
  Romero-Laorden N, Castro E
  Curr Prob Cancer 41, 251-264.
• Decline in Circulating Tumor Cell Count and Treatment Outcome in Advanced Prostate Cancer.(2016)
  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
  Eur Urol 70, 985-992.
• MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.(2016)
  Missiaglia E, Shepherd CJ, Aladowicz E, Olmos D, Selfe J, Pierron G, Delattre O, Walters Z, Shipley J
  Cancer Lett (in press).
• A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies.(2016)
  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.
  Br J Cancer 114, 889-896.
• The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer.(2016)
  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
  Oncologist 21, 716-722.
• Targeting DNA Repair: The Role of PARP Inhibition in the Treatment of Castration-Resistant Prostate Cancer.(2016)
  Castro E, Mateo J, Olmos D, de Bono JS
  Cancer J 22, 353-356.
• Impact of fusion gene status versus histology on risk-stratification for rhabdomyosarcoma: Retrospective analyses of patients on UK trials.(2016)
  Selfe J, Olmos D, Al-Saadi R, Thway K, Chisholm J, Kelsey A, Shipley J
  Pediatr Blood Cancer (in press).
• High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers.(2015)
  Castro E, Jugurnauth-Little S, Karlsson Q, Al-Shahrour F, Piñeiro-Yañez E, Van de Poll F, Leongamornlert D, Dadaev T, Govindasami K, Guy M, Eeles R, Kote-Jarai, UKGPCS, EMBRACE and IMPACT studies.
  Ann Oncol 26, 2293-2300.
• Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer.(2015)
  Scher HI, Heller G, Molina A, Attard G, Danila DC, Jia X, Peng W, Sandhu SK, Olmos D, Riisnaes R, McCormack R, Burzykowski T, Kheoh T, Fleisher M, Buyse M, de Bono JS
  J Clin Oncol 33, 1348-1355.
• Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer.(2015)
  Castro E, Goh Ch , Leongamornlert D , Saunders E, Tymrakiewicz M , Dadaev T , Govindasami K , Guy M , Ellis S , Frost D , Bancroft E , Cole T , Tischkowitz M , Kennedy MJ , Eason J , Brewer C , Gareth E, Davidson R , Eccles D , Porteous ME , Douglas F , Adlard J , Donaldson A , Antoniou AC , Kote-Jarai Z , Easton DF , Olmos D, Eeles R
  Eur Urol 68, 186-193.
• Anti-tumour activity in RAS-driven tumours by blocking AKT and MEK.(2015)
  Tolcher AW, Khan K, Ong M, Banerji U, Papadimitrakopoulou V, Gandara DR, Patnaik A, Baird RD, Olmos D, Garrett CR, Skolnik JM, Rubin EH, Smith PD, Huang P, Learoyd M, Shannon KA, Morosky A, Tetteh E, Jou YM, Papadopoulos KP, Moreno V, Kaiser B, Yap TA, Yan L, de Bono JS
  Clin Cancer Res 21, 739-748.
• A robust blood gene expression-based prognostic model for castration-resistant prostate cancer.(2015)
  Wang L, Gong Y, Chippada-Venkata U, Heck MM, Retz M, Nawroth R, Galsky M, Tsao CK, Schadt E, de Bono J, Olmos D, Zhu J, Oh WK
  BMC Med 13, 201-.
• New advances in genitourinary cancer: evidence gathered in 2014.(2015)
  Suárez C, Puente J, Gallardo E, Méndez-Vidal MJ, Climent MA, León L, Olmos D7, García del Muro X, González-Billalabeitia E, Grande E, Bellmunt J, Mellado B, Maroto P, González del Alba A
  Cancer Metast Rev 34, 443-464.
• Neutrophil to lymphocyte ratio: another drop in the ocean of CRPC biomakers?(2015)
  Castro E, Lozano R, Olmos D
  Ann Oncol 26, 622-623.
• Management of patients with advanced prostate cancer: Recommendations of the St.Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.(2015)
  Gillessen S, Omlin A, Attard G, de Bono JS, Efstathiou E, Fizazi K, Halabi S, Nelson PS, Sartor O, Smith MR, Soule HR, Akaza H, Beer TM, Beltran H, Chinnaiyan AM, Daugaard G, Davis ID, De Santis M, Drake CG, Eeles RA, Fanti S, Gleave ME, Heidenreich A, Hussain M, James ND, Lecouvet FE, Logothetis CJ, Mastris K, Nilsson S, Oh WK, Olmos D, Padhani AR, Parker C, Rubin MA, Schalken JA, Scher HI, Sella A, Shore ND, Small EJ, Sternberg CN, Suzuki H, Sweeney CJ, Tannock IF, Tombal B.
  Ann Oncol 26, 1589-1604.
• Updated recommendations from the Spanish Oncology Genitourinary Group for the treatment of patients with metastatic castration-resistant prostate cancer.(2015)
  Climent MÁ1, León-Mateos L2, González Del Alba A3, Pérez-Valderrama B4, Méndez-Vidal MJ5, Mellado B6, Arranz JÁ7, Sánchez-Hernández A8, Cassinello J9, Olmos D10, Carles J11.
  Crit Rev Oncol Hematol 96, 308-318.
• Role of vascular endothelial growth factor C in classical c.(2015)
  Rueda A, Olmos D, Vicioso L, Quero C, Gallego E, Pajares-Hachero BI, Mendiola M, Casanova M, Alvarez M, Provencio M, Alba E
  Leuk Lymphoma 56, 1286-1294.
• Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study.(2014)
  Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, Assel M, Foster CS, Mitchell G, Drew K, Mæhle L, Axcrona K, Evans DG, Bulman B, Eccles D; IMPACT Collaborators, Moss S, Eeles RA.
  Eur Urol 66, 489-499.
• DOSE-RESPONSE RELATIONSHIP IN PHASE I CLINICAL TRIALS: A EUROPEAN DRUG DEVELOPMENT NETWORK (EDDN) COLLABORATION STUDY.(2014)
  Moreno Garcia V, Olmos D, Gomez-Roca C, Cassier P, Morales-Barrera R, Del Conte G, Gallerani E, Brunetto A, Schoffski P, Marsoni S, Schellens JH, Penel N, Voest E, Evans TR, Plummer ER, Wilson RH, Soria JC, Tabernero J, Verweij J, Kaye SB
  Clin Cancer Res 20, 5663-5671.
• Circulating tumor cells: a multifunctional biomarker.(2014)
  Yap TA, Lorente D, Omlin A, Olmos D, de Bono JS
  Clin Cancer Res 20, 2553-2568.
• Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.(2014)
  Yap TA, Yan L, Patnaik A, Tunariu N, Biondo A, Fearen I, Papadopoulos K, Olmos D, Baird RD, Delgado LM, Tetteh E, Beckman RA, Lupinacci L, Riisnaes R, Decordova S, Heaton SP, Swales K, deSouza NM, Leach MO, Garrett MD, Sullivan DM, de Bono JS, Tolcher A
  Clin Cancer Res 20, 5672-5685.
• Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database(2014)
  Cassier PA, Polivka V, Judson I, Soria JC, Penel N, Marsoni S, Verweij J, Schellens JH, Morales-Barrera R, Schöffski P, Voest EE, Gomez-Roca C, Evans TR, Plummer R, Gallerani E, Kaye SB, Olmos D
  Ann Oncol 25, 1222-1228.
• Defining dose-limiting toxicity for phase 1 trials of molecularly targeted agents: Results of a DLT-TARGETT international survey.(2014)
  Paoletti X, Le Tourneau C, Verweij J, Siu LL, Seymour L, Postel-Vinay S, Collette L, Rizzo E, Ivy P, Olmos D, Massard C, Lacombe D, Kaye SB, Soria JC
  Eur J Cancer 50, 2050-2056.
• Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents – Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.(2014)
  Postel-Vinay S, Collette L, Paoletti X, Rizzo E, Massard C, Olmos D, Fowst C, Levy B, Mancini P, Lacombe D, Ivy P, Seymour L, Le Tourneau C, Siu LL, Kaye SB, Verweij J, Soria JC
  Eur J Cancer 50, 2040-2049.
• The genetic epidemiology of prostate cancer and its clinical implications.(2014)
  Eeles R, Goh C, Castro E, Bancroft E, Guy M, Al Olama AA, Easton D, Kote-Jarai Z.
  Nat Rev Urol 11, 18-31.
• Focal amplification of the androgen receptor gene in hormone-naive human prostate cancer.(2014)
  Merson S, Yang ZH, Brewer D, Olmos D, Eichholz A, McCarthy F, Fisher G, Kovacs G, Berney DM, Foster CS, Møller H, Scardino P, Cuzick J, Cooper CS, Clark JP; Transatlantic Prostate Group
  Br J Cancer 110, 1655-1662.
• Circulating and disseminated tumor cells in ovarian cancer: a systematic review.(2014)
  Romero-Laorden N, Olmos D, Fehm T, Garcia-Donas J, Diaz-Padilla I
  Gynecol Oncol 133, 632-639.
• An inflammation based score can optimize the selection of patients with advanced cancer considered for early phase clinical trials.(2014)
  Pinato DJ, Stavraka C, Flynn MJ, Forster MD, O'Cathail SM, Seckl MJ, Kristeleit RS, Olmos D, Turnbull SJ, Blagden SP
  PLoS ONE 9, e83279-.
• Randomized Phase II trial of nintedanib, afatinib and sequential combination in castration-resistant prostate cancer.(2014)
  Molife LR, Omlin A, Jones RJ, Karavasilis V, Bloomfield D, Lumsden G, Fong PC, Olmos D, O'Sullivan JM, Pedley I, Hickish T, Jenkins P, Thompson E, Oommen N, Wheatley D, Heath C, Temple G, Pelling K, de Bono JS
  Future Oncol 10, 219-231.
• Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer.(2013)
  Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, Mahmud N, Dadaev T, Govindasami K, Guy M, Sawyer E, Wilkinson R, Audern-Jones A, UKGPCS, Ellis S, Frost D, Peock S, Evans G, Tischkowitz M, Cole T, Davidson R, Eccles D, Brewer C, Douglas F, Porteous M, Donaldson A, Dorkins H, Izatt L, Cook J, Hodgson S, Kennedy J, Side L, Eason J, Murray A, Antonis A, Easton D, Kote-Jarai Z, Eeles R
  J Clin Oncol 31, 1748-1757.
• Improved survival in a cohort of trial participants with metastatic castration-resistant prostate cancer demonstrates the need for updated prognostic nomograms.(2013)
  Omlin A, Pezaro C, Mukherji D, Mulick Cassidy A, Sandhu S, Bianchini D, Olmos D, Ferraldeschi R, Maier G, Thompson E, Parker C, Attard G, de Bono J
  Eur Urol 64, 300-306.
• Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer.(2013)
  Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R, Reid AH, Attard G, Chen L, Kozarewa I, Gevensleben H, Campbell J, Fenwick K, Assiotis I, Olmos D, Yap TA, Fong P, Tunariu N, Koh D, Molife LR, Kaye S, Lord CJ, Ashworth A, de Bono J
  Ann Oncol 24, 1416-1418.
• Sarcopenia and change in body composition following maximal androgen suppression with abiraterone in men with castration-resistant prostate cancer.(2013)
  Pezaro C1, Mukherji D, Tunariu N, Cassidy AM, Omlin A, Bianchini D, Seed G, Reid AH, Olmos D, de Bono JS, Attard G
  Br J Cancer 109, 325-331.
• Clinical implications of family history of prostate cancer and genetic risk single nucleotide polymorphism (SNP) profiles in an active surveillance cohort.(2013)
  Goh CL, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Thomas K, Selvadurai ED, Woode-Amissah R, Dadaev T, Mahmud N, Castro E, Olmos D, Guy M, Govindasami K, O'Brien LT, Hall AL, Wilkinson RA, Sawyer EJ, Al Olama AA, Easton DF, Kote-Jarai Z, Parker CC, Eeles RA
  BJU Int 112, 666-673.
• A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors.(2013)
  Sandhu SK1, Papadopoulos K, Fong PC, Patnaik A, Messiou C, Olmos D, Wang G, Tromp BJ, Puchalski TA, Balkwill F, Berns B, Seetharam S, de Bono JS, Tolcher AW
  Cancer Chemoth Pharm 71, 1041-1050.
• Role of XRCC3, XRCC1 and XPD single-nucleotide polymorphisms in survival outcomes following adjuvant chemotherapy in early stage breast cancer patients.(2013)
  Castro E, Olmos D, Garcia A, Cruz JJ, González-Sarmiento R
  Clin Transl Oncol 16, 158-165.
• Prostate Cancer Screening in BRCA and Lynch Syndrome Mutation Carriers .(2013)
  Castro E1, Goh CL, Eeles RA
  Am Soc Clin Oncol Educ Book. 50, 5-.
• Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men.(2013)
  Killick E, Morgan R, Launchbury F, Bancroft E, Page E, Castro E, Kote-Jarai Z, Aprikian A, Blanco I, Clowes V, Domchek S, Douglas F, Eccles D, Evans DG, Harris M, Kirk J, Lam J, Lindeman G, Mitchell G, Pachter N, Selkirk C, Tucker K, Zgajnar J, Eeles R, Pandha H
  Sci Rep 3, 2059-.