The role of biological pathways in drug repurposing

Drug repurposing allows us to use existing drugs to treat a new disease, reducing the time and cost of developing drugs from scratch and is a key strategy to provide effective treatments against specific diseases more quickly and safely.

With the aim of optimizing the drug reuse procedure, a multidisciplinary team from the MEDAL laboratory of the Center for Biomedical Technology (CTB) of the Polytechnic University of Madrid (UPM) in Spain, has carried out research in which it is proposed an alternative to the classic paradigm based on the concept of “one drug, one target gene, one disease”, where drugs are designed specifically for specific diseases, since the development of many diseases (such as neurological disorders or heart diseases) is It is due to the involvement of different genes or biological pathways that gives rise to a much more complex mechanism.

The new study examines the potential of biological pathways as a complementary means to improve the success of drug repurposing strategies. This puts the focus on finding new treatments that are more flexible and take into account the possible involvement of different genes. This novel approach could lead to new computational methods that change the way new drug repurposing strategies are approached.

Throughout the study, the researchers conducted a comprehensive analysis of successful drug repurposing cases with the goal of identifying those cases where biological pathways serve as a fundamental framework for success. These cases are defined as DREBIOP (Drug REpurposing based on BIOlogical Pathways). Once the pathway-based reuse cases were identified, their characteristic patterns were studied considering the different biological elements associated with this data set, as well as the pathways involved. In addition, association values ​​between genes and diseases were obtained to demonstrate that the drug target gene is of lesser importance in these cases of reuse based on biological pathways.

The main results of this study show that biological pathways may be of utmost importance in certain drug repurposing processes and should be carefully considered when generating new repurposing hypotheses. Furthermore, DREBIOP cases were found to show distinguishable characteristics in terms of the number of genes, symptoms, drugs and pathways involved in the process. Also, gene-disease association values ​​between DREBIOP cases and classical cases differed statistically significantly, indicating the minor contribution of drug target genes in pathway-based drug repurposing processes.

When a drug is found to be capable of treating diseases other than the one for which it is used and designed, a significant time saving is achieved, compared to if it were a completely new drug, whose safety still needs to be verified in clinical trials. (Photo: Amazings / NCYT)

“We can conclude that the patterns obtained by this methodology can be applied to any known repositioning case and determine whether this case has occurred through biological pathways, making it a DREBIOP case. In addition, this methodology could facilitate the prioritization of possible new cases of reuse based on biological pathways by identifying the characteristic patterns that have been obtained,” says researcher Belén Otero Carrasco.

This research has been carried out as part of the doctoral thesis of the researcher Belén Otero Carrasco under the supervision of Alejandro Rodríguez González, professor at the UPM and head of the MEDAL laboratory at the CTB-UPM.

The study is titled “Identifying patterns to uncover the importance of biological pathways on known drug repurposing scenarios”. It has been published in the academic journal BMC Genomics. (Source: UPM)