An international team of scientists has discovered why some anti-tumor compounds that had been designed to show great promise are failing and have paved the way to try to make them more effective.

The study, whose findings are published in Science Advances, was led by Piero Crespo, group leader of the Cancer Network Biomedical Research Center (CIBERONC) at the Cantabrian Institute of Biomedicine and Biotechnology (IBBTEC). -northern Spain-, and Berta Casar, from the same team.

The Xosé Bustelo group, head of the CIBERONC group at the Cancer Research Center (CIC-CSIC) of Salamanca (north-west), the University of Edinburgh (United Kingdom) and the National Institutes of Health (NIH) of UNITED STATES.

About 30 percent of human tumors carry mutations in some component of a biochemical pathway made up of four proteins (RAS, RAF, MEK and ERK), which activate each other, sequentially and successively, coupling a chain of transmission through which The mechanisms necessary for cell proliferation are implemented, explained the Spanish Superior Council for Scientific Research (CSIC) in a note published this Tuesday.

In tumor cells, mutations in one of these proteins cause aberrant activation of said chain of transmission, leading to uncontrollable cell proliferation.

This pathway is so important that over the past 25 years, major pharmaceutical companies have invested billions of dollars in designing compounds by which the uncontrolled signaling that passes through it can be stopped.

And thanks to this effort, the components of this pathway currently constitute promising molecular targets towards which several antitumor drugs are directed, successfully used in the clinic for the treatment of tumors such as lung cancer, colorectal cancer and melanoma.

Several decades ago, it was discovered that mice deficient in one of these proteins (the so-called KSR) were very resistant to developing tumors, which raised the hypothesis that the inhibition of the activity of this protein could be a valid strategy for antitumor therapy.

And in 2015, a molecule (APS 2-79) appeared that blocked the activity of this protein, but its antitumor effect was very disappointing, so its clinical development was not pursued, explained the CSIC.

In the just-published work, the researchers revealed the reason for this failure, and are already working to find the appropriate inhibitors to make these antitumor compounds effective.

Categorized in: