Carmen Blanco Head of Section
T +34 917328000 (Ext 3780)
cblanco@cnio.es

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.

Publications

• Exome sequencing of plasma DNA portrays the mutation landscape of colorectal cancer and discovers mutated VEGFR2 receptors as modulators of anti-angiogenic therapies.(2018)
  Toledo RA, Garralda E, Mitsi M, Pons T, Monsech J, Vega E, Otero A, Albarran MI, Baños N, Duran Y, Bonilla V, Sarno F, Camacho Artacho M, Sánchez-Pérez T, Perea S, Alvarez R, De Martino Rodriguez A, Lietha D, Blanco-Aparicio C, Cubillo A, Dominguez O, Martínez-Torrecuadrada J, Hidalgo M.
  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)
  Toledo RA, Garralda E, Mitsi M, Pons T, Monsech J, Vega E, Otero Á, Albarran MI, Baños N, Durán Y, Bonilla V, Sarno F, Camacho-Artacho M, Sanchez-Perez T, Perea S, Álvarez R, De Martino A, Lietha D, Blanco-Aparicio C, Cubillo A, Domínguez O, Martínez-Torrecuadrada JL, Hidalgo M
  Clin Cancer Res 24, 3550-3559.
• STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.(2018)
  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
  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)
  Bejarano L, Schuhmacher AJ, Méndez-Pertuz M, Megías M, Blanco-Aparicio C, Martínez S, Pastor J, Squatrito M, Blasco MA
  Cancer Cell 32, 590-607.
• Modulation of telomere protection by the PI3K/AKT pathway.(2017)
  Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, García AB, Martínez -Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA
  Nat Commun 8, 1278-.
• Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus.(2017)
  Jiménez-García MP, Lucena-Cacace A, Robles-Frías MJ, Ferrer I, Narlik-Grassow M, Blanco-Aparicio C, Carnero A.
  Oncotarget 8, 58872-58886.
• Identification of novel PI3K inhibitors through a scaffold hopping strategy.(2017)
  Martínez González S, Hernández AI, Álvarez RM, Rodríguez A, Ramos-Lima F, Bischoff JR, Albarrán MI, Cebriá A, Hernández-Encinas E, García-Arocha J, Cebrián D, Blanco-Aparicio C, Pastor J.
  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)
  Martínez González S, Rodríguez-Arístegui S, Hernández AI, Varela C, González Cantalapiedra E, Álvarez RM, Rodríguez Hergueta A, Bischoff JR, Albarrán MI, Cebriá A, Cendón E, Cebrián D, Alfonso P, Pastor J.
  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)
  Aragoneses-Fenoll L, Montes-Casado M, Ojeda G, Acosta YY, Herranz J, Martínez S, Blanco-Aparicio C, Criado G, Pastor J, Dianzani U, Portolés P, Rojo JM
  Biochem Pharmacol 106, 56-59.
• Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.(2016)
  Mosteiro LL, Pantoja C, Alcazar N, Marión RM, Chondronasiou D, Rovira M, Fernandez-Marcos PJ, Muñoz-Martin M, Blanco-Aparicio C, Pastor J, Gómez-López G, de Martino A, Blasco MA, Abad M, Serrano M
  Science 354, pii: aaf4445.-0.
• The role of PIM1/PIM2 kinases in tumors of the male reproductive system.(2016)
  Jiménez-García MP, Lucena-Cacace A, Robles-Frías MJ, Narlik-Grassow M, Blanco-Aparicio C, Carnero A
  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)
  García-Beccaria M, Martínez P, Méndez-Pertuz M, Martínez S, Blanco-Aparicio C, Cañamero M, Mulero F, Ambrogio C, Flores JM, Megias D, Barbacid M, Pastor J, Blasco MA
  EMBO Mol Med 7, 930-949.
• Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.(2015)
  Goodson WH 3rd, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, Lasfar A, Carnero A, Azqueta A, Amedei A, Charles AK, Collins AR, Ward A, Salzberg AC, Colacci A, Olsen AK, Berg A, Barclay BJ, Zhou BP, Blanco-Aparicio C, Baglole CJ, Dong C, Mondello C, Hsu CW, Naus CC, Yedjou C, Curran CS, Laird DW, Koch DC, Carlin DJ, Felsher DW, Roy D, Brown DG, Ratovitski E, Ryan EP, Corsini E, Rojas E, Moon EY, Laconi E, Marongiu F, Al-Mulla F, Chiaradonna F, Darroudi F, Martin FL, Van Schooten FJ, Goldberg GS, Wagemaker G, Nangami G, Calaf GM, Williams G, Wolf GT, Koppen G, Brunborg G, Kim Lyerly H, Krishnan H, Ab Hamid H, Yasaei H, Sone H, Kondoh H, Salem HK, Hsu HY, Park HH, Koturbash I, Miousse IR, Scovassi AI, Klaunig JE, Vondrácek J, Raju J, Roman J, Wise JP Sr, Whitfield JR, Woodrick J, Christopher JA, Ochieng J, Martinez-Leal JF, Weisz J, Kravchenko J, Sun J, Prudhomme KR, Narayanan KB, Cohen-Solal KA, Moorwood K, Gonzalez L, Soucek L, Jian L, D'Abronzo LS, Lin LT, Li L, Gulliver L, McCawley LJ, Memeo L, Vermeulen L, Leyns L, Zhang L, Valverde M, Khatami M, Romano MF, Chapellier M, Williams MA, Wade M, Manjili MH, Lleonart M, Xia M, Gonzalez MJ, Karamouzis MV, Kirsch-Volders M, Vaccari M, Kuemmerle NB, Singh N, Cruickshanks N, Kleinstreuer N, van Larebeke N, Ahmed N, Ogunkua O, Krishnakumar PK, Vadgama P, Marignani PA, Ghosh PM, Ostrosky-Wegman P, Thompson P, Dent P, Heneberg P, Darbre P, Sing Leung P, Nangia-Makker P, Cheng QS, Robey RB, Al-Temaimi R, Roy R, Andrade-Vieira R, Sinha RK, Mehta R, Vento R, Di Fiore R, Ponce-Cusi R, Dornetshuber-Fleiss R, Nahta R, Castellino RC, Palorini R, Abd Hamid R, Langie SA, Eltom S, Brooks SA, Ryeom S, Wise SS, Bay SN, Harris SA, Papagerakis S, Romano S, Pavanello S, Eriksson S, Forte S, Casey SC, Luanpitpong S, Lee TJ, Otsuki T, Chen T, Massfelder T, Sanderson T, Guarnieri T, Hultman T, Dormoy V, Odero-Marah V, Sabbisetti V, Maguer-Satta V, Rathmell WK, Engström W, Decker WK, Bisson WH, Rojanasakul Y, Luqmani Y, Chen Z, Hu Z.
  Carcinogenesis (in press).
• Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.(2014)
  Morgado-Palacin L, Llanos S, Urbano M, Blanco-Aparicio C, Megias D, Pastor J, Serrano M
  Carcinogenesis 35, 2822-2830.
• Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.(2014)
  Moneo V, Serelde BG, Blanco-Aparicio C, Diaz-Uriarte R, Avilés P, Santamaría G, Tercero JC, Cuevas C, Carnero A
  Bmc Cancer 14, 281-.
• Genetic Modeling of PIM Proteins in Cancer: Proviral Tagging and Cooperation with Oncogenes, Tumor Suppressor Genes, and Carcinogens.(2014)
  Aguirre E, Renner O, Narlik-Grassow M, Blanco-Aparicio C
  Front Oncol 4, 109-.
• Biological characterization of ETP-46321 a selective and efficacious inhibitor of phosphoinositide-3-kinases.(2013)
  Granda TG, Cebrián D, Martínez S, Anguita PV, López EC, Link W, Merino T, Pastor J, Serelde BG, Peregrina S, Palacios I, Albarran MI, Cebriá A, Lorenzo M, Alonso P, Fominaya J, López AR, Bischoff JR
  Invest New Drug 31, 66-76.
• The PIM Family of Serine/Threonine Kinases in Cancer.(2013)
  Narlik-Grassow M, Blanco-Aparicio C, Carnero A
  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)
  Martin-Sanchez E, Rodriguez-Pinilla SM, Sanchez-Beato M, Lombardia L, Dominguez-Gonzalez B, Romero D, Odqvist L, Garcia-Sanz P, Wozniak MB, Kurz G, Blanco C, Mollejo M, Alves FJ, Menarguez J, Gonzalez-Palacios F, Rodriguez-Peralto JL, Ortiz-Romero PL, Garcia JF, Bischoff JR, Piris MA
  Haematologica 98, 57-64.
• Pim kinases in cancer: diagnostic, prognostic and treatment opportunities.(2013)
  Blanco-Aparicio C, Carnero A
  Biochem Pharmacol 85, 623-643.
• Conditional transgenic expression of PIM1 kinase in prostate induces inflammation-dependent neoplasia.(2013)
  Narlik-Grassow M, Blanco-Aparicio C, Cecilia Y, Perez M, Muñoz-Galvan S, Cañamero M, Renner O, Carnero A
  PLoS ONE 8, e60277-.