“Este contenido se encuentra unicamente en inglés”
- María Elena Hernández
Técnicos de Laboratorio
- Mª Isabel Albarrán
- Antonio Cebriá
- Elena Gómez-Casero
- Javier Klett
- Mª del Carmen Rodríguez de Miguel
In the Experimental Therapeutics Programme, we are working on both targeted and phenotypic-based drug discovery projects as well as on exploratory screening projects carried out in collaboration with other CNIO Groups. Furthermore, we conduct screenings with an ETP-antitumour library in order to identify potential new treatments in tumour types or metastatic settings for which there is an unmet medical need regarding new therapies. On the other hand, this library is used to identify novel signalling pathways that modulate a target responsible for an interesting phenotype. The newly identified signalling pathways are validated by using a chemical-biology approach, through which a set of inhibitors for the target, with quite dissimilar structures, are interrogated against the expected phenotype. In order to reach a conclusion, we establish correlations between cellular modulation of the target/pathway and the desired phenotype. Finally, the CNIO Group that develops the screening also performs all the biological validation required to confirm the new hypothesis.
- Exome sequencing of plasma DNA portrays the mutation landscape of colorectal cancer and discovers mutated VEGFR2 receptors as modulators of anti-angiogenic therapies.(2018)
Clin Cancer Res (in press).
- Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic Therapies(2018)
Clin Cancer Res 24, 3550-3559.
- STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.(2018)
Nat Med 24, 1024-1035.
- Inhibition of Trf1 telomere protein impairs tumor initiation and progression in glioblastoma multiform mouse models and patient-derived xenografts.(2017)
Cancer Cell 32, 590-607.
- Modulation of telomere protection by the PI3K/AKT pathway.(2017)
Nat Commun 8, 1278-.
- Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus.(2017)
Oncotarget 8, 58872-58886.
- Identification of novel PI3K inhibitors through a scaffold hopping strategy.(2017)
Bioorg Med Chem Lett 27, 4794-4799.
- Generation of tricyclic imidazo[1,2-a]pyrazines as novel PI3K inhibitors by application of a conformational restriction strategy.(2017)
Bioorg Med Chem Lett 27, 2536-2543.
- ETP-46321, a dual p110a/d class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis(2016)
Biochem Pharmacol 106, 56-59.
- Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.(2016)
Science 354, pii: aaf4445.-0.
- The role of PIM1/PIM2 kinases in tumors of the male reproductive system.(2016)
Sci Rep 6, 38079-.
- Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage.(2015)
EMBO Mol Med 7, 930-949.
- Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.(2015)
Carcinogenesis (in press).
- Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.(2014)
Carcinogenesis 35, 2822-2830.
- Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.(2014)
Bmc Cancer 14, 281-.
- Genetic Modeling of PIM Proteins in Cancer: Proviral Tagging and Cooperation with Oncogenes, Tumor Suppressor Genes, and Carcinogens.(2014)
Front Oncol 4, 109-.
- Biological characterization of ETP-46321 a selective and efficacious inhibitor of phosphoinositide-3-kinases.(2013)
Invest New Drug 31, 66-76.
- The PIM Family of Serine/Threonine Kinases in Cancer.(2013)
Med Res Rev 34, 136-159.
- Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas.(2013)
Haematologica 98, 57-64.
- Pim kinases in cancer: diagnostic, prognostic and treatment opportunities.(2013)
Biochem Pharmacol 85, 623-643.
- Conditional transgenic expression of PIM1 kinase in prostate induces inflammation-dependent neoplasia.(2013)
PLoS ONE 8, e60277-.