Cancer encompasses a wide spectrum of extremely complex diseases. Genetic and epigenetic modifications in tumour cells lead to the acquisition of “malignant” phenotypes that enable them to escape normal physiological control. Genome editing and transgenesis technologies are used to accurately reproduce these modifications in the mouse, creating animal models that are crucial to understand and better treat cancer. Tumour cells interact at different levels with other systems in the body such as the immune, cardiovascular or lymphatic systems, which in turn modulate tumour growth, invasion, and expansion. Behavioural factors such as diet also have an impact on cancer development. The study of such complexity demands reliable in vivo models that reproduce the features of cancer in a “whole body” context. The precise, targeted, and controlled modification of the mouse genome, using the most advanced genome editing tools, sustains the generation of genetic mouse models of cancer that are crucial for understanding the molecular basis of tumour development and the preclinical validation of new and more efficient cancer therapies.
The Unit has more than 20 years of experience in the design, generation, and validation of genetically modified mouse models using state-of-the-art genome editing techniques. It also maintains a cryoarchive of the hundreds of genetically modified mouse lines created at the CNIO
Publications
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Sayago C, Sánchez-Wandelmer J, García F, Hurtado B, Lafarga V, Prieto P, Zarzuela E, Ximénez-Embún P, Ortega S, Megías D, Fernández-Capetillo O, Malumbres M, Munoz J. (2023).Decoding protein methylation function with thermal stability analysis.. Nat Commun 14, 3016. CNIO Publication.
Lynch CJ, Bernad R, Martínez-Val A, Shahbazi MN, Nóbrega-Pereira S, Calvo I, Blanco-Aparicio C, Tarantino C, Garreta E, Richart-Ginés L, Alcazar N, Graña-Castro O, Gómez-Lopez G, Aksoy I, Muñoz-Martín M, Martinez S, Ortega S, Prieto S, Simboeck E, Camasses A, Stephan-Otto Attolini C, Fernandez AF, Sierra MI, Fraga MF, Pastor J, Fisher D, Montserrat N, Savatier P, Muñoz J, Zernicka-Goetz M, Serrano M (2020).Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases. Nat Cell Biol 22, 1223-1238. CNIO Publication.
Salazar-Roa M, Trakala M, Álvarez-Fernández M, Valdés-Mora F, Zhong C, Muñoz J, Yu Y, Peters TJ, Graña-Castro O, Serrano R, Zapatero-Solana E, Abad M, Bueno MJ, de Cedrón MG, Fernández-Piqueras J, Serrano M, Blasco MA, Wang DZ, Clark SJ, Izpisua-Belmonte JC, Ortega S, Malumbres M (2020).Transient Exposure to miR-203 Enhances the Differentiation Capacity of Established Pluripotent Stem Cells. EMBO J 39, e104324. CNIO Publication.
Blasco MT, Navas C, Martín-Serrano G, Graña-Castro O, Lechuga CG, Martín-Díaz L, Djurec M, Li Jing, Morales-Cacho L, Esteban-Burgos L, Perales-Patón J, Bousquet-Mur E, Castellano E, Jacob Harrys KC, Cabras L, Mustenau M, Drosten M, Ortega S, Mulero F, Sainz B, Dusetti N, Iovanna J, Sánchez-Bueno F, Hidalgo M, Khiabanian H, Hidalgo M, Rabadán R, Al-Shahrour F, Guerra C, Barbacid M (2019).Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF. Cancer Cell 35, 573-587. CNIO Publication.
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Open Access