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Smart bombs: drugs aiming at cancer

Cancer is the second cause of mortality in Spain and the industrialized countries. Drugs currently used in chemotherapy have serious side effects, as they act on fast-reproducing cells, both tumour and sound. However, the progressive advances in the understanding of the mechanisms that trigger the disease allow to suggest less aggressive therapies. In this vanguard field, the researchers of the University of Granada (UGR) are working on the design of new substances that can be used as selective and non-toxic anti-tumour medicines.

The research works started with one of the traditional medicines, 5-fluorouracil, “a powerful but toxic substance, still used to treat certain types of cancer such as colon”, comments Professor Joaquín Campos, one of the scientists of the group ‘Drugs research and development’, of the Faculty of Pharmacy of the UGR. The researchers added molecular structures of their own design to 5-fluorouacil that improved their efficiency as they only acted on tumour cells.

These substances were tested in a cell line of rhabdomyosarcoma, a type of muscular cancer, through the collaboration with the research team supervised by Antonia Aránega, of the UGR. It was verified that the negative effects of 5-fluoracil disappeared, at the same time that there was cell differentiation, a process in which mature cells acquire specific properties to achieve the functions they have been programmed for. Instead, tumour cells differ less than normal. It would open the possibility of reverting the process and turning tumour cells into sound ones, removing toxic elements.

Distinguishing substances
To this extent, substances were successfully tested in other tumours, such as HT-29, a colon cancer very resistant to chemotherapy. “There are many possibilities of doing the same in other cases”, maintains Campos. However, we can not talk about an only drug able to fight against any cancer, as there are more than 200 different types of tumours. The researchers from Granada focused on some of them, selected according to their prevalence –colon or breast are some of the most frequent- or other features such as their resistance to conventional treatments.

Afterwards the fragment of 5-fluorouracil was removed from the compounds and lipophilic properties increased –capacity to dissolve in fat-. “These new substances are very actice and their action mechanism is completely new”, says Campos. Having a drug capable of reverting cancer processes in tumour residues remaining after surgery or radiotherapy, “is a dream for pharmaceutical chemistry”, thinks Miguel Ángel Gallo, one of the persons in charge of the group. However, “the process until we obtain drugs based on this kind of substances will be long, at least 10 years”, he concludes.

This group is working on other drugs that attack cancer by other channel: it is about interrupting the signs that make cells avoid their programmed destruction –apoptosis- and profilerate in an uncontrolled way. According to Gallo, it has been proved that this process origins when certain defective genes, called oncogenes, give “chemical orders” to cells to reproduce instead of dying. The researchers have synthesized more than 300 compounds that interrupt the signs sent by one of these oncogenes, called ras that, according to the indications, is present in 30% of tumours.

“The problem is that we do not know all the signs that end in the nucleus, and that cells amplify these signs. Other way, we would expose ourselves to error and causality”, explains Antonio Espinosa, supervisor of the research group. According to him, the objective of doing research on ras oncogen is producing medicines to control cell division although they do not eradicate cancer. Turning the disease into chronic could improve patients´ life quality, although he still depends on medication.

Reference: Prof Antonio Espinosa. Group “Drug research and development”. Faculty of Pharmacy.
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