Research Divisions

Sarcomas and Experimental Therapies

Group LeaderLocation and ContactMembersHistory of the GroupLines of ResearchNotable PublicationsProjectsPhD ThesesPatents and Trademarks
Dr René Rodríguez
Dr René Rodríguez

René Rodríguez González

René Rodríguez obtained his PhD in Molecular Biology at the Universidad de Oviedo (Spain) in 2002, having completed part of his thesis during a period of predoctoral study at the University of Illinois in Chicago (US). Subsequently, he joined the Institute for Cancer Studies at the University of Sheffield (United Kingdom) as a post-doctoral research associate (2003-2007), where he studied DNA damage response in cancer cells. Over the following five years (2007-2012), he successively joined the Andalusian Stem Cell Bank (BACM, Granada, Spain) and the Centre for Genomics and Oncological Research (Pfizer-Universidad de Granada-Junta de Andalucía, Granada, Spain). In these two centres, he specialised in mesenchymal stem cell research and sarcoma modelling, and started to lead his own projects as a Senior Postdoctoral Researcher. Between 2012 and 2020, he held the position of senior researcher (on the Instituto de Salud Carlos III’s Miguel Servet programme) at ISPA / Hospital Universitario Central de Asturias (Oviedo, Spain), where he began to lead projects focused on exploring the relationship between stem cells and cancer in sarcomas and finding new therapeutic targets directed specifically against cancer stem cells. After completing the Miguel Servet Programme, René Rodríguez was promoted to team leader and he is currently Head of the Sarcoma and Experimental Therapeutics group at ISPA.

Sarcomas and Experimental Therapies Research Group

Edif. ISPA/FINBA, Hospital Universitario Central de Asturias
Av. de Roma s/n
33011 Oviedo, Spain.

Name Organisation Activity Euraxess classification
Blanco Lorenzo, Verónica SESPA Research/Clinical R2
Braña Vigil, Alejandro SESPA Research/Clinical R2
Costilla García, Serafín Universidad de Oviedo/SESPA Research/Teaching R3
Estupiñán Sánchez, Óscar Rafael FINBA Research R2
Gallego Martínez, Borja FINBA Research R1
González Meana, María Victoria Universidad de Oviedo Research/Teaching R3
Huergo García, Carmen Universidad de Oviedo Research R1
Murillo Cabria, Dzohara FINBA Research R1
Rey Vázquez, Verónica FINBA Research R1
Rodríguez González, René FINBA Research R4
Rodríguez Pérez, Aida María FINBA Research R2
Tornín Cavielles, Juan FINBA Research R2

ISPA Sarcomas and Experimental Therapies Research Group

How the Group was Formed

The Sarcomas and Experimental Therapies group became an Emerging ISPA Research Group in December 2019. This consolidated the sarcomas line of research that Dr René Rodríguez had initiated in 2012, when he joined the Head and Neck Cancer Research Group as a researcher on the Miguel Servet programme (Instituto de Salud Carlos III). Since then, a significant amount of multidisciplinary research has been completed within the sarcomas line of research, through eight projects financed by the Spanish National RDI Plan and other national agencies. As a result of this work, over 20 studies have been published in first quartile/decile journals in this field – such as Oncogene, Stem Cells, Stem Cell Reports, International Journal of Cancer and Journal of Clinical Medicine – three PhD theses have been completed, and three patent applications have been filed.

Summary of the Group’s Research

The group has pioneered the study of sarcomagenesis on the basis of their cell of origin . In recent years, it has managed to develop osteosarcoma, leiomyosarcoma and myxoid liposarcoma models based on mesenchymal stem cells (MSCs) that have been transformed with specific mutations [1-7]. These models have confirmed that MSCs lose their immunomodulatory capacity and take on a pro-inflammatory phenotype during tumour transformation [8]. It has also been possible to characterise a new invasion mechanism in the myxoid liposarcoma [9]. As part of our most translational research, a collection of cell lines derived from patients who underwent operations in the Central University Hospital of Asturias (HUCA) [10] has been generated, and we are evaluating the utility of this collection for personalised medicine programmes. These cell lines include the associated clinical data, and many include in-depth genome characterisation (exome and/or panel sequencing) of both the cell lines and the patient samples. Organoid and patient-derived xenograft (PDX) models are also under development. These sarcoma models and patient samples have been used to isolate and characterise the subpopulations of cancer stem cells (CSCs) by culturing sphere clones in suspension (tumour spheres) or selecting subpopulations with higher ALDH activity (aldefluor assay) and/or SOX2 and OCT4 pluripotency factors with higher transcriptional activity (SORE6 activity). As CSCs, these subpopulations have displayed a greater capacity to initiate in vivo than the cultures that were not selected. We have also confirmed that all of these CSC isolation/enrichment methods may be used to evaluate the effect of anti-tumour therapies on CSCs both in vitro and in vivo [11, 12].

As part of the group’s search for effective therapies to treat sarcomas, its studies have found that SP1-regulated transcription is altered in several sarcoma models and that blocking it with mithramycin analogue EC-8042 can efficiently inhibit tumour growth in sarcoma models and primary cell lines. Additionally, EC-8042 inhibits the expression of genes associated with the CSC phenotype and is able to eliminate CSCs not only in sarcomas but also in other types of tumours [13]. Other drugs approved for sarcoma treatment, such as trabectedin, have also displayed good anti-tumour action against CSCs, and this activity can by synergistically enhanced through combined use with the topoisomerase I inhibitor camptothecin [14]. In contrast, other compounds, such as the staurosporine analogue EC-70124, did not display any cytotoxic activity against CSCs. However, this compound was shown to be a powerful inhibitor of ABC pumps involved in drug resistance and was therefore able to synergistically increase the antitumour activity of doxorubicin [15].

      1. Rodriguez, R. et al. Cell Res 2012, 22, 62-77.
      2. Abarrategi, A. et al. Stem Cells Int 2016, 2016, 3631764.
      3. Alfranca, A. et al. Cell Mol Life Sci 2015, 72, 3097-113.
      4. Rodriguez, R. et al. Stem Cells 2013, 31, 2061-72.
      5. Rubio, R. et al. Stem Cells 2014, 32, 1136-48.
      6. Rubio, R. et al. Cancer Res 2010, 70, 4185-94.
      7. Rubio, R. et al. Oncogene 2013, 32, 4970-80.
      8. Rodriguez, R. et al. Stem Cell Reports 2014, 3, 606-19.
      9. Tornin, J. et al. Neoplasia 2018, 20, 44-56.
      10. Rey, V. et al. J Clin Med 2019, 8(4), 455-474
      11. Martinez-Cruzado, L. et al. Sci Rep 2016, 6, 27878.
      12. Menendez, ST. et al. Preprints with the Lancet. 2020.
      13. Tornin, J. et al. Oncotarget 2016, 7, 30935-50.
      14. Martinez-Cruzado, L. et al. Neoplasia 2017, 19, 460-70.
      15. Estupinan, O. et al. Int J Cancer 2019, 154, 254-266.

Current and Future Priorities

Our group performs translational research on sarcomas and the evolution of tumour subpopulations during tumour progression. We take a comprehensive approach to the study of sarcomagenesis, from initiation of tumour transformation to development and testing of new therapeutic strategies, with an increasing focus on moving towards the implementation of personalised medicine protocols. To carry out these lines of research, we have created a multidisciplinary group that brings together clinical researchers from a range of specialities (traumatology, pathology, radiology and oncology) with basic researchers trained in cell and molecular biology, biostatistics, research with animals and nanotechnology.

  • Studying the initiation of sarcomagenesis: developing mesenchymal stem cells-based sarcoma models.
  • Characterising cancer stem cell (CSC) subpopulations in human sarcomas.
  • Searching for new therapeutic targets that are effective against CSC subpopulations in sarcomas: evaluating antitumour drugs and searching for resistance mechanisms.
  • Using nanotransporters to improve the therapeutic index of antitumour drugs.
  • Developing precision medicine strategies: analysing genomic alterations in patients and developing patient-derived models for testing specific therapies.

ISPA Sarcomas Group Lines of Research

 

Key words

Sarcomas Osteosarcomas Soft tissue sarcomas
Cancer stem cells Mesenchymal stem cells Intratumour heterogeneity
Antitumour therapies Nanotransporters Personalised medicine
  • Oscar Estupiñan, Enrique Niza, Iván Bravo, Veronica Rey, Juan Tornín, Borja Gallego, Pilar Clemente-Casares, Francisco Moris, Alberto Ocaña, Verónica Blanco-Lorenzo, Mar Rodríguez-Santamaría, Aitana Vallina-Álvarez, M. Victoria González, Aida Rodríguez, Daniel Hermida-Merino, Carlos Alonso-Moreno* and Rene Rodríguez*. Mithramycin delivery systems to develop effective therapies in sarcomas. JOURNAL OF NANOBIOTECHNOLOGY (2021) 19:267 p.1-21. doi:10.1186/s12951-021-01008-x.
    IF= 10.435; 1st decile (Biotechnology & app microbiology)
  • Sofia T. Menendez, Borja Gallego, Dzohara Murillo, Aida Rodríguez and René Rodríguez*. Cancer Stem Cells as a source of drug resistance in bone sarcomas. JOURNAL OF CLINICAL MEDICINE (2021), 10:2621. doi: 10.3390/jcm10122621. (1st quartile). doi: 10.3390/jcm10122621.
    IF:  3.30; 1st quartile (Medicine, general & internal).
  • Juan Tornin, Cédric Labay, Francesco Tampieri, Maria-Pau Ginebra, Cristina Canal. Evaluation of the effects of cold atmospheric plasma and plasma-treated liquids in cancer cell cultures. NATURE PROTOCOLS. (2021) Jun;16(6):2826-2850. doi: 10.1038/s41596-021-00521-5.
    IF:  11.051; 1st decile (Biochemical research methods).
  • Ana Belén Carrillo-Gálvez, Juan Esteban Quintero, René Rodríguez, Sofía T. Menéndez, M. Victoria González, Verónica Blanco-Lorenzo, Eva Allonca, Virginia De Araujo Farias, Juan Elías González-Correa, Nadina Erill-Sagalés, Iñigo Martinez-Zubiaurre, Turid Hellevik, Juan Carlos Rodríguez-Manzaneque, Pilar Muñoz, Francisco Martin and Per Anderson. GARP promotes the proliferation and therapeutic resistance of bone sarcomas through the activation of TGF-β. 2020. CELL DEATH AND DISEASE 11(11):985. doi: 10.1038/s41419-020-03197-z.
    IF: 6.3; 1er cuartil (Cell Biology).
  • Thomas G. P. Grünewald, Marta Alonso, Sofia Avnet, Ana Banito, Stefan Burdach, Florencia Cidre-Aranaz, Gemma Di Pompo, Martin Distel, Heathcliff Dorado-Garcia, Javier Garcia-Castro, Laura González-González, Agamemnon E. Grigoriadis, Merve Kasan, Christian Koelsche, Manuela Krumbholz, Fernando Lecanda, Silvia Lemma, Dario L. Longo, Claudia Madrigal-Esquivel, Álvaro Morales-Molina, Julian Musa, Shunya Ohmura, Benjamin Ory, Miguel Pereira-Silva, Francesca Perut, Rene Rodriguez, Carolin Seeling, Nada Al Shaaili, Shabnam Shaabani, Kristina Shiavone, Snehadri Sinha, Eleni M. Tomazou, Marcel Trautmann, Maria Vela, Yvonne M. H. Versleijen-Jonkers, Julia Visgauss, Marta Zalacain, Sebastian J. Schober, Andrej Lissat, William R. English, Nicola Baldini, and Dominique Heymann. Sarcoma treatment in the era of molecular medicine. 2020. EMBO MOLECULAR MEDICINE, 12:e11131. doi: 10.15252/emmm.201911131.
    IF:  8.8; 1st decile (Medicine, research & exp)
  • Sofia T. Menendez, Veronica Rey, Lucia Martinez-Cruzado, M. Victoria Gonzalez, Alvaro Morales-Molina, Laura Santos, Verónica Blanco, Carlos Alvarez, Oscar Estupiñan, Eva Allonca, Juan Pablo Rodrigo, Javier Garcia-Castro, Juana Maria Garcia-Pedrero, and Rene Rodriguez*. SOX2 expression and transcriptional activity of pluripotency factors identify a subpopulation of cancer stem cells in sarcoma. 2020. CANCERS, 12(4), 12(4):964. doi:10.3390/cancers12040964.
    IF:  6.16; 1er cuartil (Oncology)
  • Juan Tornin, Miguel Mateu-Sanz, Aida Rodriguez, Cédric Labay, Rene Rodríguez and Cristina Canal. Pyruvate plays a main role to ensure the antitumoral selectivity of cold atmospheric plasma in osteosarcoma. 2019. SCIENTIFIC REPORTS, vol. 9(1):10681. doi: 10.1038/s41598-019-47128-1.
    IF:  4.122; 1er cuartil (multidisciplinary sciences).
  • Veronica Rey, Sofia T. Menendez, Oscar Estupiñan, Aida Rodriguez, Laura Santos, Juan Tornin, Lucía Martinez-Cruzado, David Castillo, Gonzalo R. Ordoñez, Serafin Costilla, Carlos Alvarez-Fernandez, Aurora Astudillo, Alejandro Braña and Rene Rodriguez. New chondrosarcoma cell lines with preserved stem cell properties to study the genomic drift during in vitro / in vivo growth. JOURNAL OF CLINICAL MEDICINE, 2019, 8(4), pii:E455. doi: 10.3390/jcm8040455
    IF: 5.58; 1st decile (Medicine, general & internal).
  • Jiri Hatina, Michaela Kripnerova, Katerina Hufkova, Martin Pesta, Jitka Kuncova, Jiri Sana, Ondrej Slaby, and René Rodríguez. Sarcoma stem cell heterogeneity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY, 2019, vol. 1123: 95-118. doi: 10.1007/978-3-030-11096-3_7
    IF: 1.76. 2nd quartile (Biology).
  • Oscar Estupiñan, Laura Santos, Aida Rodriguez, Lucía Fernandez-Nevado, Paula Costales, Jhudit Perez-Escuredo, Maria Ana Hermosilla, Patricia Oro, Veronica Rey, Juan Tornín, Eva Allonca, Maria Teresa Fernández-García, Carlos Alvarez-Fernández, Alejandro Braña, Aurora Astudillo, Sofia T. Menendez, Francisco Morís and Rene Rodriguez. The multikinase inhibitor EC-70124 synergistically increased the antitumor activity of doxorubicin in sarcomas. INTERNATIONAL JOURNAL OF CANCER, 2019, vol.145: 254-266. doi: 10.1002/ijc.32081
    IF: 7.36. 1st quartile (Oncology).
  • Stefano Gambera, Ander Abarrategi, Miguel A. Rodríguez-Milla, Francisca Mulero, Sofia T. Menendez, René Rodriguez, Samuel Navarro, Javier García-Castro. Role of AP-1 complex in phenotype of human osteosarcomas generated from mesenchymal stem cells. STEM CELLS, 2018, vol. 36(10):1487-1500. doi: 10.1002/stem.2869
    IF: 5.59. 1st decile (Biotechnology & app microbiology).
  • Juan Tornin, Francisco Hermida-Prado, Ranjit Singh Padda, M. Victoria Gonzalez, Carlos Alvarez-Fernandez, Veronica Rey, Lucia Martinez-Cruzado, Oscar Estupiñan, Sofia T. Menendez, Lucia Fernandez-Nevado, Aurora Astudillo, Juan P. Rodrigo, Fabrice Lucien, Yohan Kim, Hon S. Leong, Juana Maria Garcia-Pedrero and Rene Rodriguez. FUS-CHOP promotes invasion in myxoid liposarcoma through a SRC/FAK/RHO/ROCK-dependent pathway. NEOPLASIA, 2018, vol. 20(1):44-56. doi: 10.1016/j.neo.2017.11.004
    IF: 4.99. 1st quartile (Oncology).
  • Lucia Martinez-Cruzado, Juan Tornin, Aida Rodriguez, Laura Santos, Eva Allonca, Maria Teresa Fernandez-Garcia, Aurora Astudillo, Juana Maria Garcia-Pedrero and Rene Rodriguez. Trabectedin and campthotecin synergistically eliminate cancer stem cells in cell-of-origin sarcoma models. NEOPLASIA, 2017, vol. 19(6):460-470. doi: 10.1016/j.neo.2017.03.004.
    IF: 5.006 1st quartile (Oncology).
  • Lucia Martinez-Cruzado, Juan Tornin, Laura Santos, Aida Rodriguez, Javier García Castro, Francisco Morís, and Rene Rodriguez. ALDH1 expression and activity increase during tumor evolution in sarcoma cancer stem cell populations. SCIENTIFIC REPORTS, 2016, vol. 6:27878. doi: 10.1038/srep27878 .
    IF: 5.58. 1st decile (Multidisciplinary sciences).
  • Ander Abarrategi, Juan Tornin, Lucia Martinez-Cruzado, Ashley Hamilton, Enrique Martinez-Campos, Juan P. Rodrigo, M. Victoria González, Nicola Baldini, Javier Garcia-Castro and Rene Rodriguez. Osteosarcoma: cells of origin, cancer stem cells and targeted therapies. STEM CELLS INTERNATIONAL, 2016, vol. 2016, Article ID 3631764. doi:10.1155/2016/3631764.
    IF: 3.67. 2nd quartile (Cell & tissue engineering).
  • Juan Tornin, Lucia Martínez-Cruzado, Laura Santos, Aida Rodriguez, Luz-Elena Núñez, Patricia Oro, Maria Ana Hermosilla, Eva Allonca, Maria Teresa Fernández-García, Aurora Astudillo, Carlos Suarez, Francisco Moris and Rene Rodriguez. Inhibition of SP1 by the mithramycin analog EC-8042 efficiently targets tumor initiating cells in sarcoma. ONCOTARGET, 2016, vol. 7(21):30935-50. doi: 10.18632/oncotarget.8817.
    IF: 6.3. 1st decile (Oncology).
  • Arantzazu Alfranca, Lucia Martínez-Cruzado, Juan Tornín, Ander Abarrategi, Teresa Amaral, Enrique de Alava, Pablo Menéndez, Javier García-Castro and René Rodríguez. Bone microenvironment signals in osteosarcoma development. CELLULAR AND MOLECULAR LIFE SCIENCE, 2015, vol. 72(16):3097-113. doi:10.1007/s00018-015-1918-y.
    IF: 5.856. 1st quartile (Cell biology).
  • Ayudas para apoyar la actividad de grupos de investigación en el Principado de Asturias 2021-2023
    Reference No: IDI/2021/000027
    Funding Body: Gobierno del Principado de Asturias
    Amount: 750 €
    Duration: 1/1/2021 – 31/12/2023
  • Addressing drug resistance in sarcomas using patient-derived models (ADDRESS)
    Reference No: PID2019-106666RB-I00
    Funding Body: Agencia Estatal de Investigación. Proyectos de I+D+i-Retos de la Sociedad
    Amount: 217.800 € 
    Duration: 1/6/2020 – 1/6/2023
  • Addressing doxorubicin resistance in bone sarcomas using patient-derived models
    Reference No: EPIC-XS-0000203
    Funding Body: Consorcio europeo EPIC-XS / H2020
    Amount: 27.102 €
    Duration: 1/11/2020 – 31/10/2021
  • Plataformas ISCIII de apoyo a la I+D+I en Biomedicina y Ciencias de la Salud. Biobancos y biomodelos
    Reference No: PT20/00161
    Funding Body: Instituto de Salud Carlos III
    Amount: 257.400 €
    Duration: 1/06/2020 – 31/12/2022
  • Development of therapeutic strategies to target cancer stem cells subpopulations in sarcomas
    Reference No: SAF2016-75286-R
    Funding Body: Ministerio de Ciencia
    Amount: €181,000
    Duration: 1/1/2017 – 30/6/2020
  • CIBERONC (Network Biomedical Research Center: Cancer) – Instituto de Salud Carlos III
    Reference No: CB16/12/00390
    Funding Body: Instituto de Salud Carlos III
    Amount: €60,000
    Duration: 01/01/2020 – 31/12/2020
  • Grants to support the activity of research groups in the Principality of Asturias
    Reference No: IDI2018/155
    Funding Body: Gobierno del Principado de Asturias
    Amount: €180,000
    Duration: 01/01/2020 – 31/12/2020
  • Strategy of precision medicine in sarcomas based on the use of primary cultures derived from patients
    Reference No: GEIS-62
    Funding Body: Grupo Español de Investigación en Sarcomas (Spanish Sarcoma Research Group)
    Amount: €15,000
    Duration: 1/10/2017 – 31/9/2019
  • Setting the dosage and efficacy studies of indolocarbazole EC-70124 in predictive animal models (INDOLKIN)
    Reference No: RTC-2016-4603-1
    Funding Body: Ministerio de Ciencia
    Amount: €1,257,858
    Duration: 01/03/2016 – 30/06/2019
  • Cancer stem cells in sarcomas: searching for new therapeutic targets
    Reference No: SAF2013-42946-R
    Funding Body: Ministerio de Ciencia
    Amount: €145,200
    Duration: 01/01/2014 – 31/12/2016
  • Cancer stem cells in sarcomas: searching for new therapeutic targets
    Reference No: COF13-007
    Funding Body: Gobierno del Principado de Asturias
    Amount: €24,000
    Duration: 01/01/2014 – 31/12/2014
  • Tumour initiating cells (TICs) and cancer stem cells (CSCs) in sarcomas: generating human mesenchymal stromal/stem cell (MSC)-based sarcoma models to provide new therapeutic targets
    Reference No: CP11/00024
    Funding Body: Instituto de Salud Carlos III
    Amount: €121,500
    Duration: 01/01/2012 – 31/03/2015
  • Desarrollo de nuevas estrategias terapéuticas con actividad antitumoral en sarcomas basadas en el uso de indolocarbazoles y derivados de la mitramicina
    PhD Student: Oscar R. Estupiñán Sánchez
    Supervisors: René Rodríguez González / María Matos González
    Classification: Sobresaliente cum laude y Mención internacional
    Date: 10 de Diciembre del 2021
  • Optimización de la selección de pacientes con carcinoma hepatocelular a tratamiento con quimioembolización transarterial hepática (TACE)
    PhD Student: María Pipa Muñiz
    Supervisors: Serafín Costilla García / María Varela
    Classification: Sobresaliente cum laude
    Date: 16 de Julio del 2021
  • El uso del triptófano en el tratamiento de los sofocos, astenia e insomnio en pacientes con cáncer de próstata, mama y cérvico-uterino
    PhD Student: Johanna del Carmen Peña Vivas
    Supervisors: Serafín Costilla García / German J. Juan Rijo
    Classification: Sobresaliente cum laude
    Date: 16 de Septiembre del 2021
  • Estimación volumétrica hepática en una población europea occidental a partir de pruebas de imagen y su relación con medidas antropométricas. Utilidad en la evaluación de candidatos a trasplante hepático.
    PhD Student:  Jose Manuel Fernandez-Carrera Soler
    Supervisor: Serafin Costilla
    Classification: Sobresaliente cum laude por Unanimidad
    Date: 16 de Junio de 2019
  • Characterisation of molecular alterations in a human myxoid liposarcoma model generated from mesenchymal stem cells
    PhD Student: Juan Tornín Cavielles
    Supervisor: René Rodríguez González
    Classification: Summa cum laude
    Date: 29/6/2017
  • Cancer stem cells in sarcomas: the anti-tumour effect of trabectedin
    PhD Student: Lucía Martínez Cruzado
    Supervisor: René Rodríguez González
    Classification: Summa cum laude
    Date: 07/07/2017
  • A method for predicting or forecasting the response to cancer treatment
    Inventors: Per Anderson, Ana Belen Carrillo-Galvez, Francisco Martín and René Rodríguez González
    Application No: P202030147
    Priority Country: Spain
    Priority Date: 21/02/2020
    Owners: Servicio Andaluz de Salud (Andalusian Health Service); Fundación Progreso y Salud (Progress and Health Foundation); FINBA-ISPA
  • Compositions for treating cancer, and specifically sarcomas
    Inventors: Per Anderson, Ana Belen Carrillo-Galvez, Francisco Martín and René Rodríguez González
    Application No: P202030148
    Priority Country: Spain
    Priority Date: 21/02/2020
    Owners: Servicio Andaluz de Salud; Fundación Progreso y Salud; FINBA-ISPA