They identify a therapeutic target for treating metastatic and resistant prostate cancer


Posted 12/05/2018 15:06:39CET


Researchers at the Institute of Biomedical Research of Bellvitge (Idibell) and the Catalan Institute of Oncology (ICO) have identified a new vulnerability to attack in metastatic and more aggressive prostate tumors that have become resistant to available hormonal therapies.

The study, published in the journal Nature Communications & # 39; and also involving researchers from Columbia University and the University of Bern, Switzerland, opens the door to a new combination therapy to treat this type of cancer, reported this article. Wednesday the Idibell and the ICO.

Researchers have shown that these tumors generate increasing levels of NSD2 protein as tumor progression progresses and acquisition of resistance to therapies, and have been able to validate experimentally that these tumors, to continue growing and spreading, are dependent on this protein. , then represents an emerging therapeutic target.

They used a series of lines of transgenic mice that carry mutations prevalent in prostate cancer patients, who are only active in rodent prostate epithelial cells, as is the case in the vast majority of patients.

Based on these models, once the mice developed cancer, cells from both primary prostate tumors and metastases were isolated and patterns of gene expression were analyzed.


Through the use of bioinformatics tools, researchers have identified candidate genes to represent a vulnerability in these aggressive tumors and factors that are differentially present in malignancy and metastasis.

NSD2 is a protein with enzymatic activity that introduces chemical modifications in proteins that give structural support to the DNA strands, called histones.

The modifications in these histones produced by the action of NSD2 provoke a relaxation in the levels of compression of the DNA strands, triggering the activation of the expression of a set of genes with tumorigenic potential.

One of the main hypotheses of the researchers signing this study is that the activation of these genes as a result of the action of NSD2 is responsible for the resistance to the chemotherapeutic treatments that are generally given to cancer patients. Prostate

The researchers work with molecules that allow inhibit the function of NSD2 and thus decrease the malignancy of prostate tumors in mice, and this translates into an increase in survival of the experimental model.

They believe that inhibition of this protein could lead to the resensitisation of prostate tumors that are resistant to the usual antiandrogenic treatments.


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