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Precision Medicine

Galician Oncological Research Group (GIO)

Fernando Domínguez Puente
Group Leader | Full Professor
fernando.dominguez@usc.es
 
Lab: P1L1
Field of knowledge

Cancer is a global health problem responsible for one in six deaths worldwide. It´s estimated that the number of cancer cases in Europe increase from 2.8 million in 2020 to 3.4 million in 2040 (GLOBOCAN 2020). This highlights the importance of the prevention and the development of safe and efficient cancer treatments. Our laboratory is focused on the study of the mechanism of action of an entirely novel class of metal molecules, the sub-nanometer clusters of 5 atoms of Ag (Ag5). 
Ag5 is characterized by its small size (<1nm), which is responsible for the loss of its typical metallic character and the acquisition of a molecular-like behaviour. Ag5 catalyzes the selective oxidation of the thiol groups of glutathione (GSH) and the thioredoxin (Trx) family of proteins mediated by reactive oxygen species (ROS) within a cell. Since redox homeostasis is fundamental to maintaining normal cellular functions and ensuring cell survival, Ag5 cause rapid cell death by induction of apoptosis in cells with high levels of ROS such as cancer cells. Initial in vivo studies, using a lung cancer mice model that metastasizes to the mediastinal lymph nodes, showed the ability of Ag5 to reach both primary tumour and metastases and to significantly decrease their size without causing additional toxic effects (Porto, V., et al, 2022).

Research Lines

The group's research activity has as a main objective the understanding of the mechanism of action of Ag5 and their potential use as an anticancer drug. More specifically, the group is currently working on the following research lines:

  1.  Investigate the mechanism of action of Ag5 using cancer cell lines and animal models.
  2. Combination with chemotherapy. Combining Ag5 with therapeutic agents that are demonstrated effective in clinic should provide better therapeutic effects without additional toxicity.
  3. Evaluation of the radiosensitizing properties of Ag5. Using cancer cell lines, we are testing the effect of the combination of Ag5 and standard RT (X-rays), Proton radiotherapy and Carbon ions radiotherapy (CIRT).  

Members

Blanca Domínguez Loidi
Research Associate
blanca.dominguez@usc.es
Nerea Davila Ferreiria
Postdoctoral research associate
n.davila@nanogap.es
Vanesa Porto González
Research Associate
vanesa.porto@usc.es

Selected publications

Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand

M. Isabel Acuña, Ana R. Rubio, Marta Martínez-Alonso, Natalia Busto, Ana María Rodríguez, Nerea Davila-Ferreira, Carl Smythe, Gustavo Espino, Begoña García and Fernando Domínguez

Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols

Vanesa Porto,David Buceta,Blanca Domínguez,Carmen Carneiro,Erea Borrajo,María Fraile,Nerea Davila-Ferreira,Iria R. Arias,José M. Blanco,Maria C. Blanco,Juan M. Devida,Lisandro J. Giovanetti,Félix G. Requejo,Juan C. Hernández-Garrido,José J. Calvino,Miguel López-Haro,Giampaolo Barone,Andrew M. James,Tomás García-Caballero,Diego M. González-Castaño,Martin Treder,Wolfgang Huber,Anxo Vidal,Michael P. Murphy,M. Arturo López-Quintela, Fernando Domínguez

Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort.

Paula Silva-Rodríguez, Manuel Bande, Daniel Fernández-Díaz, Nerea Lago-Baameiro, María Pardo, María José Blanco-Teijeiro, Fernando Domínguez, Lourdes Loidi, Antonio Piñeiro.

A Simple Entropic-Driving Separation Procedure of Low-Size Silver Clusters, Through Interaction with DNA.

David Buceta, Blanca Dominguez, Sara Vieitez, Iria R. Arias, J. Manuel Ageitos, M. Carmen Blanco, Giampaolo Barone, Fernando Domínguez, M. Arturo López-Quintela.

New half-sandwich ruthenium(ii) complexes as proteosynthesis inhibitors in cancer cells

Ballester, FJ; Ortega, E; Porto, V; Kostrhunova, H; Davila-Ferreira, N; Bautista, D; Brabec, V; Dominguez, F; Santana, MD; Ruiz, J

Thiabendazole-based Rh(III) and Ir(III) biscyclometallated complexes with mitochondria-targeted anticancer activity and metal-sensitive photodynamic activity.

Cristina Pérez-Arnaiz, María Isabel Acuña, Natalia Busto, Igor Echevarría, Marta Martínez-Alonso, Gustavo Espino, Begoña García, Fernando Domínguez.

Selected Results

Projects

National project(s)

Advanced dosimetry for novel radiotherapy approaches in brain tumors (DOSE BRAIN)
REF: PLEC2022-009476Duration: -
PI: Faustino Gómez Rodríguez
AGENCIA ESTATAL DE INVESTIGACION
Advanced dosimetry for novel radiotherapy approaches in brain tumors (DOSE BRAIN).
REF: PLEC2022-009476Duration: -
PI: Faustino Gómez Rodríguez
AGENCIA ESTATAL DE INVESTIGACION
Investigación de clústeres moleculares terapéuticos como tratamiento senolítico para la Covid - 19
REF: CPP2021-008680Duration: -
PI: Fernando Domínguez Puente
AGENCIA ESTATAL DE INVESTIGACION

Spin-Offs

Arjuna Therapeutics

Arjuna Therapeutics is a therapeutic platform bringing transformational science to the field of oncology and other disease states.

Patents

Combination of Atomic Quantum Clusters (AQCs) and antineoplasic drugs, and its use in the prevention and/or treatment of cell proliferative disorders
Aplication Nº: WO2011EP69400 20111104
Therapeutic uses of Atomic Quantum Clusters
Aplication Nº: EP18196959
Conjugates comprising nanoparticles coated with platinum containing compounds.
Aplication Nº: WO2010069941A1
Víctor Franco Puentes, Fernando Domínguez Puente, Francisco Manuel Romero Martínez, Óscar gallego Rubio.
Methods and reagents for the detection of biomolecules using luminiscence.
Aplication Nº: PCT/EP2013/076452
Manuel Arturo Lopez QuintelaFernando Dominguez PuenteJose Ma Jimeno Donaque
Methods for diagnosing follicular thyroid cancer
Aplication Nº: US20120184452A1
María del Carmen Pastoriza Rodríguez, María del Carmen Carneiro Freire, José Manuel Cameselle-Teijeiro, Fernando Domínguez Puente, Anxo Vidal Figueroa.
Use of Atomic Quantum Clusters (AQCs) in the prevention autoimmune diseases.
Aplication Nº: WO2012059571
Manuel Arturo López Quintela, Fernando Domínguez Puente.
Use of Atomic Quantum Clusters (AQCs) in the prevention of viral infections.
Aplication Nº: WO2012059570A1
Manuel Arturo González Quintela, Fernando Domínguez Puente.
Use of Atomic Quantum Clusters (AQCs) in the prevention of cell proliferative disorders, viral infections and autoimmune diseases.
Aplication Nº: EP2457572A1
Manuel Arturo López Quintela, Fernando Domínguez Puente
Diagnosis of cancer and other proliferative disorders by analysis of prothymosin alpha expression.
Aplication Nº: US 07/694800
Fernando Domínguez Puente