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

Brain metastasis is the most common neurological complication of cancer. When metastatic cells reach the brain, prognosis is poor given that local therapies ( i.e. surgery and radiation ) have limited benefits for patients and the disease inevitably progresses. The rise in the number of patients with brain metastasis is partially due to the increasing number of systemic therapies that work extra-cranially but are unable to provide the same therapeutic benefit in the brain. Consequently, cancer cells present at this secondary site have additional time to evolve and to grow into clinically detectable lesions. In the laboratory, 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 in order to challenge the current status of this unmet clinical need.

Publications

• Er EE, Valiente M, Ganesh K, Zou Y, Agrawal S, Hu J, Griscom B, Rosenblum M, Boire A, Brogi E, Giancotti FG, Schachner M, Malladi S, Massagué J (2019). Author Correction: Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat Cell Biol 21, 480.
• Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX (2019). Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 27, 1277-1292.
• Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Martínez L, Martínez-Saez E, Cajal SRY, Megías D, Hernández-Encinas E, Blanco-Aparicio C, Martínez L, Zarzuela E, Muñoz J, Fustero-Torres C, Pineiro E, Hernández-Laín A, Bertero L, Poli V, Sánchez-Martínez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med 24, 1024-1035.
• Er EE, Valiente M, Ganesh K, Zou Y, Agrawal S, Hu J, Griscom B, Rosenblum M, Boire A, Brogi E, Giancotti FG, Schachner M, Malladi S, Massagué J (2018). Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat Cell Biol 20, 966-978.
• Mustafa DAM, Pedrosa RMSM, Smid M, van der Weiden M, de Weerd V, Nigg AL, Berrevoets C, Zeneyedpour L, Priego N, Valiente M, Luider TM, Debets R, Martens JWM, Foekens JA, Sieuwerts AM, Kros JM (2018). T lymphocytes facilitate brain metastasis of breast cancer by inducing Guanylate-Binding Protein 1 expression. Acta Neuropathol 135, 581-599.
• Verdura S, Cuyàs E, Llorach-Parés L, Pérez-Sánchez A, Micol V, Nonell-Canals A, Joven J, Valiente M, Sánchez-Martínez M, Bosch-Barrera J, Menendez JA (2018). Silibinin is a direct inhibitor of STAT3. Food Chem Toxicol 116, 161-172.
• Preusser M, Winkler F, Valiente M, Manegold C, Moyal E, Widhalm G, Tonn JC, Zielinski C (2018). Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion. ESMO OPEN 3, e000262.
• Valiente M, Ahluwalia MS, Boire A, Brastianos PK, Goldberg SB, Lee EQ, Le Rhun E, Preusser M, Winkler F, Soffietti R (2018). The Evolving Landscape of Brain Metastasis. Trends in Cancer 4, 176-196.
• Bartolini G, Sánchez-Alcañiz JA, Osório C, Valiente M, García-Frigola C, Marín O (2017). Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons.. Cell Reports 18, 1157-1170.
• Wasilewsky D, Priego N, Fustero-Torre C, Valiente M (2017). Reactive Astrocytes in Brain Metastasis. Front Oncol 7, 298.
• Chen Q, Boire A, Jin X, Valiente M, Er EE, Lopez-Soto A, Jacob LS, Patwa R, Shah H, Xu K, Cross JR, Massagué J (2016). Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer.. Nature 533, 493-498.
• Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ, Chaft JE, Kris MG, Huse JT, Brogi E, Massagué J (2014). Serpins promote cancer cell survival and vascular co-option in brain metastasis.. Cell 156, 1002-1016.
• Vanharanta S, Marney CB, Shu W, Valiente M, Zou Y, Mele A, Darnell RB, Massagué J (2014). Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer.. Elife 4, e02734.