Galician Oncological Research Group (GIO)
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).
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Líneas de investigación
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:
- Investigate the mechanism of action of Ag5 using cancer cell lines and animal models.
- Combination with chemotherapy. Combining Ag5 with therapeutic agents that are demonstrated effective in clinic should provide better therapeutic effects without additional toxicity.
- 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).
Publicaciones seleccionadas
Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand
Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols
Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort.
A Simple Entropic-Driving Separation Procedure of Low-Size Silver Clusters, Through Interaction with DNA.
New half-sandwich ruthenium(ii) complexes as proteosynthesis inhibitors in cancer cells
Thiabendazole-based Rh(III) and Ir(III) biscyclometallated complexes with mitochondria-targeted anticancer activity and metal-sensitive photodynamic activity.