An obstacle to cancer cells
The circulation of cancer cells through the blood vessels is often the cause of metastasis. These cancer cells contaminate normal cells and the pathology spreads throughout the body. Metastasis is the main risk in cancers. In order to prevent this process from occurring, a team from the Chemistry Faculty at the Donostia-San Sebastián campus of the University of the Basque Country (UPV-EHU) analysed the connections between cancer and normal cells.
Diminutive in order to be stealthy
Concretely, the UPV-EHU analysed the proteins that are involved in these connections. From amongst these proteins, they chose the ones that have a single active centre. If this centre is blocked, the cancer cell will not be able to adhere itself to a healthy cell and, thus, this path of spreading the disease is blocked.
The first thing to do is to analyse the structure of the proteins chosen. This task is undertaken using computers, given that the proteins are gigantic molecules. Once the structure is analysed and with the data for the active centre of the connection, the design of a new, small molecule to block this centre is initiated.
The new molecule must have very special characteristics, the main one being its size: so that our immunological system does not detect it, it has to be very small; if the new synthesised molecule is any bigger, our immunological system will detect and destroy it.
Also, this new diminutive molecule must adhere itself to the active centre of the protein and, in order to do this, it has to comply to a series of requirements, i.e. it must imitate the naturally-occurring molecule that connects to the active centre.
Using all these characteristics, a series of molecules - a family of new molecules - is designed and then synthesised. It has to be taken into account that these molecules have not been created previously and do not exist naturally and, consequently, it is not known if they are stable or not.
The final step is to verify that the new synthesised molecules carry out their job.
To block and to die
First of all, trials are carried out in vitro. Here the new molecules are analysed for their capacity to adhere to the protein and neutralise it. If a cancer cell is unable to unite with a healthy cell and contaminate it, it enters a programmed stage of death and self-destructs. Moreover, as a range of molecules has been designed and developed, it has to be known which give the best results and which are the most active.
The most active molecule in the in vitro trials have to demonstrate subsequently that they are also the most active in vivo, and often the results can vary. It is possible for another molecule from the same family to have better results in vivo; thus, it is vital to carry out these trials.
Once the series of trials are over, it can be decided to enhance the molecule’s efficacy or, if the results are very good, the process to convert it into medication can be initiated. But this is not the task of chemists; their job now is to follow another line of research to design more new molecules to combat other protein cancer cell connections.
Garazi Andonegi | alfa