More effective antitumor strategies

Kortabitarte Egiguren, Irati

Elhuyar Zientzia

One of the biggest current problems in cancer treatment is that tumor cell destruction agents are highly toxic to the patient's healthy cells and tissues. To address this problem, UPV/EHU works to find more specific treatments and to study the differences between tumor cells and healthy cells.
More effective antitumor strategies
01/10/2007 | Kortabitarte Egiguren, Irati | Elhuyar Zientzia Komunikazioa
Cells not treated with retinoids (left image) and treated (right).
(Photo: UPV)

A team of researchers from the Faculty of Medicine and Dentistry works to find pharmacological agents that improve the therapeutic benefit of some of the therapies used for the treatment of oncological diseases: chemotherapy, immunotherapy and radiation therapy.

The aim of this team of researchers is to identify compounds that affect metabolic pathways and processes that occur differently in healthy and diseased tissues. That is, they want to make a selective selection to increase the sensitivity of treatment in diseased tissues and, at the same time, avoid damage to healthy cells and tissues.

In this sense, researchers study different biological modulators in some models of tumors such as melanoma, sarcoma, and colon cancer. On the one hand, the use of agents to modulate glutation level (GSH) has been studied. In fact, glutathione is a basic element in the biological processes that occur in cells, both in healthy cells and in tumor cells. Tumor cells with a high level of IMS have a higher capacity for growth and metastasis development, while at the same time having a lower sensitivity to antitumor agents compared to healthy cells. On the other hand, agents that promote cell separation such as retinoids have been used. This is because tumor cells lose their usual degree of separation, so instead of playing a certain role they tend to reproduce and grow.

More selective therapies

The two groups of agents mentioned above have been combined with the usual agents in antitumor therapies and have verified the benefits obtained. On the one hand, it has been proven that one of the agents that modulates the level of GSH, oxothiazolidine carboxylate (OTZ), makes antitumor agents more effective and at the same time does not harm healthy tissue. Another agent that modulates the level of GSH is butionin sulfoxamide (SMI). It has been proven that when the latter is combined with conventional antitumor agents, it also affects healthy tissue, although it increases the effectiveness of standard drugs.

On the other hand, the UPV/EHU research team uses retinoids for tumor cell separation and recovery from a situation similar to that of healthy cells combined with traditional standard agents. Tumor cells' response to retinoids depends on their degree of separation. In general, tumor cells with a very low degree of separation have a higher sensitivity to retinoids. For their part, tumor cells with low degree of separation, attending to retinoids, can activate defense mechanisms that increase the level of glutathione, which tend to increase metastasis.

Melanoma cells marked with an SMI level analysis indicator.

It is a very interesting fact. In fact, so far they have not described that in the same type of tumor cell lines could have such a different behavior. In this sense, UPV researchers have somehow joined the two modulating lines, the modulating GSH and the modulators that drive cell differentiation. That is, the relationship between the two has been studied and it has been proven that retinoids, in addition to promoting cell separation, modulate the level of GSH of tumor cells.

UPV researchers continue to investigate the administrative guidelines and appropriate concentrations of the agents used. In biological modulation, these two elements are very important to ensure treatment success. All this biological modulation does not depend on quantity, that is, the more, the better. The optimal response is obtained at a certain concentration and it is necessary to find that optimal dose. Lack and abuse can be counterproductive.

UPV-EHU researchers investigate both in vitro and in vivo in UPV/EHU laboratories. One of the main objectives of this group of researchers is that in the future all the information obtained from these research can be applied to clinical sessions.

Project overview
Identification of biological modulators that will improve the therapeutic benefit of some therapies used for the treatment of oncological diseases: chemotherapy, immunotherapy and radiation therapy.
Ana Alonso Varona and Teodoro Palomares Married.
Working team
A. Alonso, T. Palomares, I. García-Alonso, P. Bilbao, J. González, R. Sanisidro, M. Candy, I. Diaz and J. Marquez.
Cellular Biology and Histology and Surgery, Radiology and Physical Medicine.
Medicine and Dentistry.
UPV/EHU, Department of Health of the Basque Government and Etortek Program.
Ana Alonso and Teodoro Palomares.
(Photo: I. Kortabitarte)
Kortabitarte Egiguren, Irati
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