Angiogenesis and tumor malignization Lab

Oriol Casanovas- Group Leader
Gabriela Jimenez Valerio - Postoc
Jordi Senserrich Velasco - Postdoc
Roser Pons Cursach - PhD student
Iratxe Zuazo Gaztelu - PhD student
Nicklas Bassani - PhD student
Mariona Bartrolí Comellas - PhD student
Júlia Salaberry Pinto - MSc student
  • Description
  • Publications
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Angiogenesis, or formation of new blood vessels from other pre-existing vessels, is essential for the tumour growth, progression and the subsequent appearance of metastases in other organs. For all these reasons, in recent years, the anti-angiogenic therapies have been a point of intense research in developing new cancer treatments. More than 50 pharmacological inhibitors of angiogenesis are currently at different points of its clinical development. Most of the targets for these compounds are different factors that induce angiogenesis. One of the most important is the specific vascular endothelial growth factor (VEGF), which stimulates the proliferation and migration of endothelial cells and the formation of new blood vessels. In fact, the first selective inhibitor of angiogenesis that has been approved for use in patients is bevacizumab (Avastin), a neutralizing antibody against VEGF.
Despite these benefits, as in most systemic therapies, resistance to antiangiogenic treatments occurs, involving both upfront refractoriness (intrinsic resistance), and acquired resistance that is gained over the duration of the treatment.
The focus of our research is the tumour adaptation to the anti-angiogenic therapies, particularly focusing on the VEGF/R path, both in cancer in animal models and in cancer patients. The specific lines of research in our group cover several aspects:

1) the mechanisms of tumour adaptation that result in resistance to these therapies, and

2) the tumor adaptation to these therapies that lead to increase the invasion and the production of more metastasis (malignant tumour).

The applicability of our research has been focused on renal tumors and neuroendocrine tumours, since they are typically treated with antiangiogenic therapies and can benefit from the preclinical results.
Original publications by the group

  • Jiménez-Valerio G, Casanovas O. (2017) "Angiogenesis and Metabolism: Entwined for Therapy Resistance." Trends in Cancer, 3(1):10-18.
          IF: nn  (Q1)

  • Duran I, Lambea J, Maroto P, González-Larriba JL, Flores L, Granados-Principal S, Graupera M, Sáez B, Vivancos A, Casanovas O. (2017) "Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action." Target Oncol. 12(1):19-35.
          IF: nn  (Q1)

  • Jiménez-Valerio G, Casanovas O. (2016) "Antiangiogenic resistance via metabolic symbiosis." Mol Cell Oncol. 3(5):e1211979.
          IF: nn  (Q1)

  • Jiménez-Valerio G, Martínez-Lozano M, Bassani N, Vidal A, Ochoa-de-Olza M, Suárez C, García-del-Muro X, Carles J, Viñals F, Graupera M, Indraccolo S, and Casanovas O. (2016) "Resistance to Antiangiogenic Therapies by Metabolic Symbiosis in Renal Cell Carcinoma PDX Models and Patients" Cell Reports, 15(6): 1134–1143.
           IF: 8.0  (Q1)

  • Jiménez-Valerio G, Casanovas O. (2016) "Antiangiogenic resistance: Novel angiogenesis axes uncovered by antiangiogenic therapies research." Current Drug Targets, 17(15):1728-1734.
          IF: 3.03  (Q1)

  • Casanovas O, Salazar R, Tabernero J. (2014) "Multi-target angiokinase inhibitors to fight resistance." Cell Cycle 13:17, 2649-2650.
          IF: 5.4  (Q1)

  • Moserle L, Jiménez-Valerio G, & Casanovas O. (2014) “Antiangiogenic Therapies: Going Beyond Their Limits” Cancer Discovery, 4(1):31-41.
          IF: 15.9 (Q1)

  • Moserle L, Casanovas O. (2013) "Anti-angiogenesis and metastasis: a tumour and stromal cell alliance" J Intern Med. 273(2):128-37.
          IF: 5.8 (Q1)

  • Teulé A & Casanovas O. (2012) “Relevance of Angiogenesis in Neuroendocrine Tumors” Targeted Oncology, 7(2):93-8.
           IF: 3.3 (Q1)

  • Casanovas O. (2012) “Cancer: Limitations of therapies exposed” Nature, 484(7392):44-6.
          IF: 38.6 (Q1)

  • Moserle L & Casanovas O. (2012) “Exploiting pleiotropic activities of semaphorins as multi-target therapies for cancer “ EMBO Molecular Medicine, 4(3):168-70.
          IF: 7.8 - 10.3 (Q1)

  • Casanovas O. (2011) "The Adaptive Stroma Joining the Anti-angiogenic Resistance Front". Journal of Clinical Investigation, 121(4): 1244-1247.
           IF: 13.1 (Q1)

  • Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, Inoue M, Bergers G, Hanahan D* & Casanovas O*. (2009) “Anti-angiogenic therapy elicits malignant progression of tumours to increased local invasion and distant metastasis”. Cancer Cell, 15(3):220-31.  
          IF: 25.3 (Q1)

Colaboration articles

  • Mateo F, Arenas EJ, Aguilar H, Serra-Musach J, de Garibay GR, …, Casanovas O, … Gomis RR, Pujana MA. (2016) "Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition." Oncogene, doi: 10.1038/onc.2016.427.
    IF: nn  (Q1)

  • Soler A, Figueiredo AM, Castel P, Martin L, Monelli E, Angulo-Urarte A, Mila-Guasch M, Viñals F, Baselga J, Casanovas O, Graupera M. (2016) " Therapeutic benefit of selective inhibition of p110α PI3-kinase in pancreatic neuroendocrine tumors" Clinical Cancer Research, 22(23):5805-5817.
    IF: 8.0  (Q1)

  • Capdevila J, Casanovas O, Salazar R, Castellano D, Segura A, Fuster P, Aller J, García-Carbonero R, Jimenez-Fonseca P, Grande E, Castaño JP. (2016) "Translational research in neuroendocrine tumors: pitfalls and opportunities." Oncogene, doi: 10.1038/onc.2016.316.
    IF: nn  (Q1)

  • Gahete MD, Rincón-Fernández D, Durán-Prado M, Hergueta-Redondo M, Ibáñez-Costa A, Rojo-Sebastián A, Gracia-Navarro F, Culler MD, Casanovas O, Moreno-Bueno G, Luque RM, Castaño JP. (2016) "The truncated somatostatin receptor sst5TMD4 stimulates the angiogenic process and is associated to lymphatic metastasis and disease-free survival in breast cancer patients." Oncotarget, 7(37):60110-60122.
    IF: nn  (Q1)

  • Alsina-Sanchis E, Figueras A, Lahiguera Á, Vidal A, Casanovas O, Graupera M, Villanueva A, Viñals F. (2016) "The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels." Int J Cancer, 139(8):1894-903.
    IF: nn  (Q1)

  • Johansson JD, Mireles M, Morales-Dalmau J, Farzam P, Martínez-Lozano M, Casanovas O, Durduran T. (2016) "Scanning, non-contact, hybrid broadband diffuse optical spectroscopy and diffuse correlation spectroscopy system." Biomedical Optics Express. 7(2):481-98.
    IF: 3.45  (Q1)

  • Soriano A, París-Coderch L, Jubierre L, Martínez A, Zhou X, Piskareva O, Bray I, Vidal I, Almazán-Moga A, Molist C, Roma J, Bayascas JR, Casanovas O, Stallings RL, Sánchez de Toledo J, Gallego S, Segura MF. (2016) "MicroRNA-497 impairs the growth of chemoresistant neuroblastoma cells by targeting cell cycle, survival and vascular permeability genes" Oncotarget 7(8):9271-87.
    IF: 6.05  (Q1)

  • Serra H, Chivite I, Angulo-Urarte A, Soler A, Sutherland JD, Arruabarrena-Aristorena A, Ragab A, Lim R, Malumbres M, Fruttiger M, Potente M, Serrano M, Fabra À, Viñals F, Casanovas O, Pandolfi PP, Bigas A, Carracedo A, Gerhardt H, Graupera M. (2015) "PTEN mediates Notch-dependent stalk cell arrest in angiogenesis". Nature Commun. 6:7935.
    IF: 10.6  (Q1)

  • Grande E, Capdevila J, Castellano D, Teulé A, Durán I, Fuster J, Sevilla I, Escudero P, Sastre J, García-Donas J, Casanovas O, Earl J, Ortega L, Apellaniz-Ruiz M, Rodriguez-Antona C, Alonso-Gordoa T, Díez JJ, Carrato A, García-Carbonero R. (2015) "Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)." Ann Oncol. 26(9):1987-93.
    IF: 6.5  (Q1)

  • Martínez-Høyer S, Solé-Sánchez S, Aguado F, Martínez-Martínez S, Serrano-Candelas E, Hernández JL, Iglesias M, Redondo JM, Casanovas O, Messeguer R, Pérez-Riba M. (2015) "A novel role for an RCAN3-derived peptide as a tumor suppressor in breast cancer." Carcinogenesis. 36(7):792-9.
    IF: 5.6  (Q1)

  • Batista S, Maniati E, Reynolds LE, Tavora B, Lees DM, Fernandez I, Elia G, Casanovas O, Celso CL, Hagemann T, Hodivala-Dilke K. (2014) "Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis" Nature Commun. 5:5054.
    IF: 10.x  (Q1)

  • Larrayoz M, Pio R, Pajares MJ, Zudaire I, Ajona D, Casanovas O, Montuenga LM, Agorreta J. (2014) "Contrasting responses of non-small cell lung cancer to antiangiogenic therapies depend on histological subtype." EMBO Mol Med. 6(4):539-50.
    IF: 8.8  (Q1)

  • Capdevila J, Meeker A, García-Carbonero R, Pietras K, Astudillo A, Casanovas O, Scarpa A. (2014) "Molecular biology of neuroendocrine tumors: from pathways to biomarkers and targets." Cancer Metastasis Rev. 33(1):345-351.
    IF: 6.4 (Q1)

  • Juliachs M, Muñoz C, Moutinho C, Vidal A, Condom E, Esteller M, Graupera M, Casanovas O, Germa JR, Villanueva A, Vinals F. (2014) "The PDGFRβ-AKT Pathway Contributes To CDDP-Acquired Resistance In Testicular Germ Cell Tumors" Clin Cancer Res. 20(3):658-67.
    IF: 8.3 (Q1)

  • Soler A, Serra H, Pearce W, Angulo A, Guillermet-Guibert J, Friedman LS, Viñals F, Gerhardt H, Casanovas O, Graupera M, Vanhaesebroeck B. (2013) "Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis" J Exp. Medicine,  210(10):1937-45.
    IF: 13.9 (Q1)

  • Juliachs M, Vidal A, Del Muro XG, Piulats JM, Condom E, Casanovas O, Graupera M, Germà JR, Villanueva A, Viñals F. (2013) "Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors" BMC Cancer, 13:382.
    IF: 3.3 (Q1)

  • Vives M, Ginestà MM, Gracova K, Graupera M, Casanovas O, Capellà G, Serrano T, Laquente B, Viñals F. (2013) "Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells". Int J Cancer,  133(10):2464-72.
    IF: 5.0 (Q1)

  • Öberg KE, Casanovas O, Castaño JP, Chung DC, Delle Fave G, Denefle P, Harris P, Khan MS, Kulke MH, Scarpa A, Tang LH, Wiedenmann B. (2013) "Molecular Pathogenesis of Neuroendocrine Tumors: Implications for Current and Future Therapeutic Approaches". Clin Cancer Res. 19(11):2842-2849.
    IF: 8.2 (Q1)

  • Anderberg C, Cunha SI, Zhai Z, Cortez E, Pardali E, Johnson JR, Franco M, Páez-Ribes M, Cordiner R, Fuxe J, Johansson BR, Goumans MJ, Casanovas O, Ten Dijke P, Arthur HM, Pietras K. (2013) "Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination" J Exp Medicine. 210(3):563-79.
    IF: 13.9 (Q1)

  • Juliachs M, Castillo-Ávila W, Vidal A, Piulats JM, Del Muro XG, Condom E, Hernández-Losa J, Teixidó C, Pandiella A, Graupera M, Casanovas O, Germà JR, Villanueva A, Viñals F. (2013) "ErbBs inhibition by lapatinib blocks tumor growth in an orthotopic model of human testicular germ cell tumor" Int J Cancer. 133(1):235-46.
    IF: 5.0 (Q1)

  • da Silva-Diz V, Solé-Sánchez S, Valdés-Gutiérrez A, Urpí M, Riba-Artés D, Penin RM, Pascual G, González-Suárez E, Casanovas O, Viñals F, Paramio JM, Batlle E, Muñoz P. (2012) "Progeny of Lgr5-expressing hair follicle stem cell contributes to papillomavirus-induced tumor development in epidermis". Oncogene, 32(32):3732-43.
    IF: 8.5 (Q1)

  • Maione F, Capano S, Regano D, Zentilin L, Giacca M, Casanovas O, Bussolino F, Serini G & Giraudo E (2012) “Semaphorin 3A overcomes cancer hypoxia and metastatic dissemination induced by anti-angiogenic treatment in mice” Journal of Clinical Investigation, 122(5):1832-48.
    IF: 13.4 (Q1)

  • Benedito R, Woeste M, Zamykal M, Radtke F, Duarte A, Rocha S, Casanovas O, Pytowski B & Adams RH. (2012) “Notch-dependent VEGFR3 upregulation enables angiogenesis without VEGF/VEGFR2 signalling” Nature, 484(7392):110-4.
    IF: 38.6 (Q1)

  • Franco M, Pàez-Ribes M, Cortez E, Casanovas O, Pietras K. (2011) "Use of a Mouse Model of Pancreatic Neuroendocrine Tumors to Find Pericyte Biomarkers of Resistance to Anti-angiogenic Therapy" Hormone and Metabolic Research, 43(12):884-9.
    IF: 2.6 (Q1)

  • Martinez-Poveda B, Gomez V, Alcaide-German M, Perruca S, Vazquez S, Alba LE, Casanovas O, Garcia-Bermejo ML, Peso L, Jimenez B. (2011) "Non-invasive monitoring of hypoxia-inducible factor activation by optical imaging during antiangiogenic treatment in a xenograft model of ovarian carcinoma" International Journal of Oncology, 39(3):543-52.
    IF: 2.4 (Q2)

  • Nardo G, Favaro E, Curtarello M, Moserle L, Zulato E, Persano L, Rossi E, Esposito G, Crescenzi M, Casanovas O, Sattler U, Mueller-Klieser W, Biesalski B, Thews O, Canese R, Iorio E, Zanovello P, Amadori A, Indraccolo S. (2011) "Glycolytic Phenotype and AMP Kinase Modify the Pathologic Response of Tumor Xenografts to VEGF Neutralization" Cancer Research, 71(12):4214-4225.
    IF: 7.9 (Q1)

  • Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R, Ivan C, Rossi S, Setien F, Casanovas O, Simo-Riudalbas L, Carmona J, Carrere J, Vidal A, Aytes A, Puertas S, Ropero S, Kalluri R, Croce CM, Calin GA, Esteller M. (2011) "Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing" Proc Natl Acad Sci U S A, 108(11):4394-9.
    IF: 9.7 (Q1)

  • Balart J, Pueyo G, de Llobet LI, Baro M, Sole X, Marin S, Casanovas O, Mesia R, Capella G. (2011) “The use of caspase inhibitors in pulsed-field gel electrophoresis may improve the estimation of radiation-induced DNA repair and apoptosis.” Radiation Oncology, 6(1):6.
    IF: 2.5 (Q1)

  • Del Valle-Pérez B, Martínez VG, Lacasa-Salavert C, Figueras A, Shapiro SS, Takafuta T, Casanovas O, Capellà G, Ventura F, Viñals F. (2010) "Filamin B plays a key role in vascular endothelial growth factor-induced endothelial cell motility through its interaction with Rac-1 and Vav-2." The Journal of Biological Chemistry, 285(14):10748-60.
    IF: 5.3 (Q1)

  • Castillo-Avila W, Piulats JM, Garcia Del Muro X, Vidal A, Condom E, Casanovas O, Mora J, Germà JR, Capellà G, Villanueva A, Viñals F. (2009) "Sunitinib inhibits tumour growth and synergizes with Cisplatin in orthotopic models of Cisplatin-sensitive and Cisplatin-resistant human testicular germ cell tumours". Clinical Cancer Research, 15(10):3384-95.
     IF: 6.7 (Q1)

  • Laquente B., Lacasa C., Ginestà M.M., Casanovas O., Figueras A., Galán M., Ribas I.G., Germà J.R., Capellà G. and Viñals F. (2008) "Antiangiogenic effect of gemcitabine following metronomic administration in a pancreas cancer model". Molecular Cancer Therapeutics, 7(3):638-47.
  • IF: 5.0 (Q1)

  • Durán I., Salazar R., Casanovas O., Arrazubi V., Vilar E., Siu L., Yao J. and Tabernero J. (2007) “New drug development in digestive neuroendocrine tumours” Annals of Oncology, 18(8):1307-13.
    IF: 4.9 (Q1)

FUNDING

Título. Coordinated Development of Inhibitors and Biomarkers for Resistance to Antiangiogenics in Cancer (AngioResist) Referencia. ERC-PoC-2015-713503
Entidad Financiadora. H2020 – European Research Council (ERC)
Investigador Principal. Oriol Casanovas, ICO-IDIBELL
Fecha. 2016-2018
Cuantía de la Subvención.  149.932 €
 
Título. Nuevas dianas en angiogénesis tumoral para bloquear la revascularización y la resistencia terapéutica (ANGIORESIST) Referencia. SAF2012-36575
Entidad Financiadora. Ministerio de Educación y Ciencia
Investigador Principal. Oriol Casanovas, ICO-IDIBELL
Fecha. 2013-2015
Cuantía de la Subvención. 193.050 €
 
Título. Stromal Contribution to Tumor Malignization after Anti-Angiogenic Therapies - (STROMALIGN) Referencia. ERC-StG-2012-281830
Entidad Financiadora. FP7 – European Research Council (ERC)
Investigador Principal. Oriol Casanovas, ICO-IDIBELL
Fecha. 2013-2017
Cuantía de la Subvención.  1.495.796 €
 
Título. “A Pilot Project for Personalized Cancer Medicine: Oncoprofile” Referencia. PIE13/00022
Entidad Financiadora. Ministerio de Sanidad
Coordinador (Global IP). Manel Esteller, IDIBELL
Investigador (IP). Oriol Casanovas, ICO-IDIBELL
Duración. 2014-2016
Cuantía de la Subvención. TOTAL: 770.000 € (60.309 € para O.Casanovas)
 
Título. “Interacción Tumor-Estroma y Resistencia a anti-tumorales (ITERT)”. Referencia. 2014-SGR-725
Entidad Financiadora. AGAUR, Generalitat de Catalunya.
Investigador Principal y Coordinador. Oriol Casanovas, ICO-IDIBELL
Fecha. 2014-2016
Cuantía de la Subvención. 28.800 €
 
Título. “Malignización tumoral en el tratamiento antiangiogénico: Mecanismos y nuevas dianas”. Referencia. SAF2009-08375
Entidad Financiadora. Ministerio de Ciencia e Innovación
Investigador Principal. Oriol Casanovas, ICO-IDIBELL
Fecha. 2010-2012
Cuantía de la Subvención. 254.100 €
 
Título. “Estudio molecular y funcional de la invasión tumoral en el tratamiento anti-angiogénico contra el cáncer”. Referencia. SAF2006-00590
Entidad Financiadora. Ministerio de Educación y Ciencia
Investigador Principal. Oriol Casanovas, ICO-IDIBELL
Fecha. 2007-2009
Cuantía de la Subvención. 135.883 €

PATENTS
Autores: Casanovas O, Jiménez-Valerio G, Ochoa-de-Olza M, Martínez-Lozano M.
Referencia: PCT/EP2016/055182
Título: “METHODS AND COMPOSITIONS FOR THE TREATMENT OF ANTI-ANGIOGENIC RESISTANT CANCER”
Países de prioridad: Paises Europeos del PCT                        Fecha: 11-Marzo-2015
Entidad titular: ICO y IDIBELL (co-titulares)
Empresas Explotando: ---
 
Autores: Casanovas O, Jiménez-Valerio G, Ochoa-de-Olza M, Navarro-Pérez V, Bassani N, Verdaguer H.
Referencia: PCT/EP2016/055143
Título: “PD-ECGF AS BIOMARKER OF CANCER”
Países de prioridad: Paises Europeos del PCT                        Fecha: 11-Marzo-2015
Entidad titular: ICO y IDIBELL (co-titulares)
Empresas Explotando: ---


To inquiere about open positivas please contact:

​Dr. Oriol Casanovas
Program Against Cancer Therapeutic Resistance, ProCURE
Catalan Institute of Oncology
Bellvitge Biomedical Research Institute, IDIBELL
3 floor, LRT1, Hospital Duran i Reynals
Gran Via 199-203, 08907 L’Hospitalet de Llobregat
​