They discover a mechanism to attack treatment-resistant prostate cancers


12/04/2023 at 17:21


The basis of clinical research is based on trying to find out why some therapeutic targets, which are normally found through genetic analysis of the tumor, respond to treatments and others do not.

The fight against prostate cancer, the most common tumor in men, has made giant strides thanks to the detection of PSA (prostate-specific antigen) blood analysis, which facilitates early diagnosis and cure for the majority of patients. However, there are tumors that do not respond to hormonal, radiotherapy or chemotherapy treatments, including some of those called castration-resistant, which are aggressive and especially resistant to treatments.

The research could also be used against other types of cancer and against degenerative diseases.

But a team led by researchers from IRB Barcelona (Biomedical Research Institute), Xavier Salvatella and Antoni Riera, in which Dr. Denes Hnisz (from the Max Plank Institute of Molecular Genetics) and Dr. Marianne D. Sadar (from BC Cancer of the University of British Columbia) participated. Columbia, Canada), has found a new approach to stopping these very dangerous cancers, a mechanism that could also serve against other types of tumors and against some degenerative diseases.

The basis of clinical research, in which cell and mouse modelsis based on trying to find out why some therapeutic targets, which are normally found through genetic analysis of the tumor, respond to treatments and others do not (they are ‘undruggable’, the term used in English).

The androgen receptor

One of the main reasons that these targets do not respond is when they have proteins that are intrinsically disordered, meaning they lack a clear three-dimensional structure. However, they have a tendency to form condensates molecular. Among them is the androgen receptor (a protein in prostate cells) which, in the case of cancer, participates in the activation of tumor cells.

“The research opens new possibilities to address unmet medical needs,”

Xavier Salvatella

Head of the biophysics laboratory at IRB Barcelona

The research, which has been published in the journal ‘Nature Structural & Molecular Biology’, has discovered that the mechanisms involved in condensation could serve to inhibit receptor activity of androgens, which is fundamental in prostate cancer and responsible for “some tumors adapting and no longer being sensitive to treatments,” according to Dr. Salvatella.

Application to other diseases

The discovery opens the door to new therapeutic avenues in cancer or other diseases where proteins are intrinsically disordered. “The logic we have followed to optimize an androgen receptor inhibitor could be explored to inhibit other proteins, opening up new possibilities to address unmet medical needs,” says Salvatella, head of the molecular biophysics laboratory at IRB Barcelona.

However, in addition to trying to address other targets that do not respond to treatments, so that research becomes a new therapy against prostate cancer needs to be developed drugs targeting those disordered proteins that undergo molecular condensation. To this end, Salvatella, together with other specialists, has created the company Neuge Therapeuticis, which is carrying out essays drug screening in patients.