Brain Metastasis Group

Manuel Valiente Group Leader
T +34 (+34) 917 328 000 (Ext 3530)
mvaliente@cnio.es

Research Scientists

Raul Bardini

Post-Doctoral Fellows

Mariam Al-Masmudi
Neibla Priego

Graduate Students

Jimena Benzal
Ana De Pablos
Carolina Hernández
Irene Salgado
Juan José Vázquez

Technicians

Laura Adriana Álvaro
Pedro García
Diana Patricia Retana
Oliva Ana Sánchez
Catalina Vela

Brain metastasis is the most common neurological complication of cancer and, in spite of the progress made with local (i.e., surgery and radiation) and systemic (i.e., targeted therapy, immunotherapy) therapies, prognosis remains poor. Indeed, the increased incidence of brain metastases is partially due to systemic therapies that work extra-cranially, but do not provide the same therapeutic benefit in the brain. We study why and how cells from different cancer types (breast cancer, lung cancer, and melanoma) are able to access the brain, survive, and colonise this vital organ. We dissect the biology of these processes in vivo using experimental models and patient-derived material to challenge this unmet clinical need. Our research has identified novel brain metastasis mediators, characterised the metastasis-associated microenvironment, designed better experimental models, and explored novel methods to target brain metastasis as well as to prevent or revert the frequent impact of metastasis on brain function.

Publications

Hwang WL, Perrault EN, Birbrair A, Mattson BJ, Gutmann DH, Mabbott DJ, Cukierman E, Repasky EA, Sloan EK, Zong H, Demir IE, Saloman JL, Borniger JC, Hu J, Dietrich J, Breunig JJ, Çifcibaşı K, Ahmad Kasm KA, Valiente M, Wintermark M, Acharya MM, Scheff NN, D'Silva NJ, Vermeer PD, Wong RJ, Talbot S, Hervey-Jumper SL, Wang TC, Ye Y, Pan Y, Bunimovich YL, Amit M. (2025). Integrating priorities at the intersection of cancer and neuroscience. Cancer Cell 43, 1-5. CNIO Publication.
Pisano F, Masmudi-Martín M, Andriani MS, Cid E, Kazemzadeh M, Pisanello M, Balena A, Collard L, Parras TJ, Bianco M, Baena P, Tantussi F, Grande M, Sileo L, Gentile F, De Angelis F, De Vittorio M, Menendez de la Prida L, Valiente M, Pisanello F. (2025). Vibrational fiber photometry: label-free and reporter-free minimally invasive Raman spectroscopy deep in the mouse brain. Nat Methods 22, 371-379. CNIO Publication.
Priego N, de Pablos-Aragoneses A, Perea-García M, Pieri V, Hernandez-Oliver C, Alvaro-Espinosa L, Rojas A, Sanchez O, Steindl A, Caleiras E, Garcia F, Garcia-Martin S, Grana-Castro O, Garcia-Mulero S, Serrano D, Velasco-Beltran P, Jimenez-Lasheras B, Egia-Mendikute L, Rupp L, Stammberger A, Meinhardt M, Chaachou-Charradi A, Martínez-Saez E, Bertero L, Cassoni P, Mangherini L, Pellerino A, Ruda R, Soffietti R, Al-Shahrour F, Saftig P, Sanz-Pamplona R, Schmitz M, Crocker SJ, Calvo A, Palazon A, Group R, Valiente M. (2025). TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis acting on infiltrating CD8+ T cells. Cancer Discovery 15, 179-201. CNIO Publication.
Steindl A, Valiente M. (2025). Potential of ex vivo organotypic slice cultures in neuro-oncology. Neuro-Oncology 27, 338-351. CNIO Publication.
Cómitre-Mariano B, Segura-Collar B, Vellila-Alonso G, Contreras R, Henandez-Lain A, Valiente M, Sepulveda JM, Marcus SG, García-Posadas G, Jiménez-Roldán L, Perez-Nuñez Á, Gargini R. (2025). S100A proteins show a spatial distribution of inflammation associated with the glioblastoma microenvironment architecture. Theranostics 15, 726-744. Publication in other institutions.
Masmudi-Martín M, Oller-Salvia B, Perea M, Teixidó M, Valiente M, Giralt E, Sánchez-Navarro M. (2025). A Site-Specific MiniAp4-Trastuzumab Conjugate Prevents Brain Metastasis. Mol Pharmacol 22, 1384-1395. CNIO Publication.
Anders CK, Van Swearingen AED, Neman J, Joyce JA, Cittelly DM, Valiente M, Zimmer AS, Floyd SR, Dhakal A, Sengupta S, Ahluwalia MS, Nagpal S, Kumthekar PU, Emerson S, Basho R, Beal K, Moss NS, Razis ED, Yang JT, Sammons SL, Sahebjam S, Tawbi HA. (2025). Consortium for Intracranial Metastasis Academic Research (CIMARa): Global interdisciplinary collaborations to improve outcomes of patient with brain metastases. Neurooncol Adv 7, vdaf049. CNIO Publication.
Amit M, Anastasaki C, Dantzer R, Demir IE, Deneen B, Dixon KO, Egeblad M, Gibson EM, Hervey-Jumper SL, Hondermarck H, Magnon C, Monje M, Na'ara S, Pan Y, Repasky EA, Scheff NN, Sloan EK, Talbot S, Tracey KJ, Trotman LC, Valiente M, Van Aelst L, Venkataramani V, Venkatesh HS, Vermeer PD, Winkler F, Wong RJ, Gutmann DH, Borniger JC. (2024). Next Directions in the Neuroscience of Cancers Arising outside the CNS. Cancer Discovery 14, 669-673. CNIO Publication.
Raymant M, Astuti Y, Alvaro-Espinosa L, Green D, Quaranta V, Bellomo G, Glenn M, Chandran-Gorner V, Palmer DH, Halloran C, Ghaneh P, Henderson NC, Morton JP, Valiente M, Mielgo A, Schmid MC. (2024). Macrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer. Nat Commun 15, 3593. CNIO Publication. Open Access
Dankner M, Maritan SM, Priego N, Kruck G, Nkili-Meyong A, Nadaf J, Zhuang R, Annis MG, Zuo D, Nowakowski A, Biondini M, Kiepas A, Mourcos C, Le P, Charron F, Inglebert Y, Savage P, Théret L, Guiot MC, McKinney RA, Muller WJ, Park M, Valiente M, Petrecca K, Siegel PM. (2024). Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes. Neuro-Oncology 26, 1502-1066. CNIO Publication.
Jagust P, Powell AM, Ola M, Watson L, de Pablos-Aragoneses A, García-Gómez P, Fallon R, Bane F, Heiland M, Morris G, Cavanagh B, McGrath J, Ottaviani D, Hegarty A, Cocchiglia S, Sweeney KJ, MacNally S, Brett FM, Cryan J, Beausang A, Morris P, Valiente M, Hill ADK, Varešlija D, Young LS (2024). RET overexpression leads to increased brain metastatic competency in luminal breast cancer.. J Natl Cancer I 116, 1632-1644. CNIO Publication.
Sanchez-Aguilera A, Masmudi-Martín M, Navas-Olive A, Baena P, Hernández-Oliver C, Priego N, Cordón-Barris L, Alvaro-Espinosa L, García S, Martínez S, Lafarga M; RENACER; Lin MZ, Al-Shahrour F, Menendez de la Prida L, Valiente M (2023). Machine learning identifies experimental brain metastasis subtypes based on their influence on neural circuits. Cancer Cell 41, 1637-1649. CNIO Publication. Open Access
Zheng D, Pisano F, Collard L, Balena A, Pisanello M, Spagnolo B, Mach-Batlle R, Tantussi F, Carbone L, De Angelis F, Valiente M, de la Prida LM, Ciracì C, De Vittorio M, Pisanello F. (2023). Toward Plasmonic Neural Probes: SERS Detection of Neurotransmitters through Gold-Nanoislands-Decorated Tapered Optical Fibers with Sub-10 nm Gaps. Adv Mater 35, e2200902. CNIO Publication. Open Access
Ocaña-Tienda B, Pérez-Beteta J, Jiménez-Sánchez J, Molina-García D, Ortiz de Mendivil A, Asenjo B, Albillo D, Pérez-Romasanta LA, Valiente M, Zhu L, García-Gómez P, González-Del Portillo E, Llorente M, Carballo N, Arana E, Pérez-García VM. (2023). Growth exponents reflect evolutionary processes and treatment response in brain metastases. npj Syst. Biol. Appl. 9, 35. CNIO Publication. Open Access
Valiente M, Ortega-Paino E (2023). Updating cancer research with patient-focused networks. Trends in Cancer (in press). CNIO Publication. Open Access
Valiente M, Sepúlveda JM, Pérez A. (2023). Emerging targets for cancer treatment: S100A9/RAGE.. ESMO OPEN 8, 100751. CNIO Publication.
Zhu L, Miarka L, Baena P, Perea-García M, Valiente M. (2023). Protocol to generate murine organotypic brain cultures for drug screening and evaluation of anti-metastatic efficacy. Star Protocols 4, 102194. CNIO Publication.
Cátia Monteiro, Lauritz Miarka, María Perea-García, Neibla Priego, Pedro García-Gómez , Laura Álvaro-Espinosa, Ana de Pablos-Aragoneses, Natalia Yebra, Diana Retana, Patricia Baena, Coral Fustero-Torre, Osvaldo Graña-Castro, Kevin Troulé, Eduardo Caleiras, Patricia Tezanos, Pablo Muela, Elisa Cintado , José Luis Trejo, Juan Manuel Sepúlveda , Pedro González-León , Luis Jiménez-Roldán , Luis Miguel Moreno , Olga Esteban , Ángel Pérez-Núñez, Aurelio Hernández-Lain, José Mazarico Gallego, Irene Ferrer, Rocío Suárez, Eva M. Garrido-Martín, Luis Paz-Ares, Celine Dalmasso, Elizabeth Cohen-Jonathan Moyal, Aurore Siegfried, Aisling Hegarty, Stephen Keelan, Damir Varešlija, Leonie S. Young, Malte Mohme, Yvonne Goy, Harriet Wikman, Jose Fernández-Alén, Guillermo Blasco, Lucía Alcázar, Clara Cabañuz, Sergei I. Grivennikov, Andrada Ianus , Noam Shemesh, Claudia C. Faria, Rebecca Lee , Paul Lorigan , Emilie Le Rhun, Michael Weller, Riccardo Soffietti, Luca Bertero , Umberto Ricardi, Joaquim Bosch-Barrera , Elia Sais, Eduard Teixidor, Alejandro Hernández-Martínez, Alfonso Calvo, Javier Aristu, Santiago M. Martin, Alvaro Gonzalez, Omer Adler, Neta Erez, RENACER* and Manuel Valiente (2022). Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism. Nat Med 28, 752-765. CNIO Publication. Open Access
Zheng D, Pisano F, Collard L, Balena A, Pisanello M, Spagnolo B, Mach-Batlle R, Tantussi F, Carbone L, De Angelis F, Valiente M, Prida L, Ciracì C, De Vittorio M, Pisanello F. (2022). Toward Plasmonic Neural Probes: SERS Detection of Neurotransmitters through Gold Nanoislands-decorated Tapered Optical fibers with sub-10 nm Gaps. Adv Mater (in press). CNIO Publication. Open Access
Zhu L, Retana D, García-Gómez P, Álvaro-Espinosa L, Priego N, Masmudi-Martín M, Yebra N, Miarka L, Hernández-Encinas E, Blanco-Aparicio C, Martínez S, Sobrino C, Ajenjo N, Artiga MJ, Ortega-Paino E, Torres-Ruiz R, Rodríguez-Perales S; RENACER, Soffietti R, Bertero L, Cassoni P, Weiss T, Muñoz J, Sepúlveda JM, González-León P, Jiménez-Roldán L, Moreno LM, Esteban O, Pérez-Núñez Á, Hernández-Laín A, Toldos O, Ruano Y, Alcázar L, Blasco G, Fernández-Alén J, Caleiras E, Lafarga M, Megías D, Graña-Castro O, Nör C, Taylor MD, Young LS, Varešlija D, Cosgrove N, Couch FJ, Cussó L, Desco M, Mouron S, Quintela-Fandino M, Weller M, Pastor J, Valiente M. (2022). A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. EMBO Mol Med 14, 14552. CNIO Publication. Open Access
Masmudi-Martín M, Zhu L, Sanchez-Navarro M, Priego N, Casanova-Acebes M, Ruiz-Rodado V, Giralt E, Valiente M. (2021). Brain metastasis models: What should we aim to achieve better treatments?. Adv Drug Deliver Rev 169, 79-99. CNIO Publication.
Zhu L, Retana D, García-Gómez P, Álvaro-Espinosa L, Priego N, Masmudi-Martín M, Yebra N, Miarka L, Hernández-Encinas E, Blanco-Aparicio C, Martínez S, Sobrino C, Ajenjo N, Artiga MJ, Ortega-Paino E, Torres-Ruiz R, Rodríguez-Perales S, RENACER, Soffietti R, Bertero L, Cassoni P, Weiss T, Muñoz J, Sepúlveda JM, González-León P, Jiménez-Roldán L, Moreno LM, Esteban O, Pérez-Núñez A, Hernández-Laín A, Toldos O, Ruano Y, Alcázar L, Blasco G, Fernández-Alén J, Caleiras E, Lafarga M, Megías D, Graña-Castro O, Nör C, Taylor MD, Young LS, Varešlija D, Cosgrove N, Couch FJ, Cussó L, Desco M, Weller M, Pastor J, Valiente M (2021). A drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent local relapse and treat established brain metastasis. EMBO Mol Med (in press). CNIO Publication.
Pisano F, Kashif MF, Balena A, Pisanello M, De Angelis F, de la Prida LM, Valiente M, D'Orazio A, De Vittorio M, Grande M, Pisanello F (2021). Plasmonics on a neural implant: engineering light-matter interactions on the nonplanar surface of tapered. Adv Opt Mater (in press). CNIO Publication.
Álvaro-Espinosa L, de Pablos-Aragoneses A, Valiente M, Priego N. (2021). Brain Microenvironment Heterogeneity: Potential Value for Brain Tumors.. Front Oncol 11, 714428. CNIO Publication. Open Access
Jablonska PA, Bosch-Barrera J, Serrano D, Valiente M, Calvo A, Aristu J. (2021). Challenges and Novel Opportunities of Radiation Therapy for Brain Metastases in Non-Small Cell Lung Cancer. Cancers 13, 2141. CNIO Publication. Open Access
Miarka L, Valiente M (2021). Animal models of brain metastasis. Neurooncol Adv 3, v144-v156. CNIO Publication. Open Access
Boire A, Brastianos PK, Garzia L, Valiente M (2020). Brain metastasis. Nat Rev Cancer 20, 4-11. CNIO Publication.
de Pablos-Aragoneses A, Valiente M (2020). An Inbred Ecosystem that Supports Medulloblastoma.. Immunity 52, 431-433. CNIO Publication. Open Access
Pe?rez-Garci?a VM, Calvo GF, Bosque JJ, Leo?n-Triana O, Jime?nez J, Pe?rez- Beteta J, Belmonte-Beitia J, Valiente M, Zhu L, Garci?a-Go?mez P, Sa?nchez-Go?mez P, Herna?ndez-San Miguel E, Hortigu?ela R, Azimzade Y, Molina-Garci?a D, Marti?nez A, Acosta- Rojas A, Ortiz de Mendivil A, Valette F, Schucht P, Murek M, Pe?rez-Cano M, Albillo D, Honguero Marti?nez AF, Jime?nez London?o GA, Arana E, Garci?a Vicente AM (2020). Universal scaling laws rule explosive growth in human cancers.. Nat Phys 16, 1232-1237. CNIO Publication. Open Access
Valiente M, Van Swearingen AED, Anders CK, Bairoch A, Boire A, Bos PD, Cittelly DM, Erez N, Ferraro GB, Fukumura D, Gril B, Herlyn M, Holmen SL, Jain RK, Joyce JA, Lorger M, Massague J, Neman J, Sibson NR, Steeg PS, Thorsen F, Young LS, Varešlija D, Vultur A, Weis-Garcia F, Winkler F (2020). Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines. Cancer Res 80, 4134-4323. CNIO Publication. Open Access
Vilariño N, Bruna J, Bosch-Barrera J, Valiente M, Nadal E (2020). Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic. Cancer Treat Rev 89, 102067. CNIO Publication.
García-Gómez P, Valiente M (2020). Vascular Co-Option in Brain Metastasis. ANGIOGENESIS 23, 3-8. CNIO Publication.
Ramón Y Cajal S, Sancho P, Soucek L, Peinado H, Abad M, Valiente M, Efeyan A, Pardo J, Quesada V, Jimeno J, Duque PM, Antón A, Varela I, Schuhmacher AJ (2020). A spotlight on cancer researchers in Spain: new paradigms and disruptive ideas. Clin Transl Oncol 22, 798-801. CNIO Publication.
Valiente M*, de la Prida* (2020). Breaking down the wall: the strategic plan of cancer to conquer the brain.. Epilepsy Curr (in press). CNIO Publication.