The prostate cancer it is the most common non-cutaneous cancer in men worldwide. According to international estimates, about one in six men will develop prostate cancer in his lifetime, and worldwide, more than 375,000 patients will die from it each year. Tumor resistance to current therapies plays an essential role in this and new approaches are therefore urgently needed.
Now an international research team from the University of Bern, Inselspital Bern and the University of Connecticut has identified a previously unknown weakness in prostate cancer cells. This weak spot is probably also present in other cancer cells.
The study was led by Mark Rubin of the Department of Biomedical Research (DBMR) and Center for Precision Medicine (BCPM) of the University of Bern and Inselspital Bern, and by Rahul Kanadia of the Department of Physiology and Neurobiology and the Institute of systems genomics at the University of Bern. the University of Connecticut.
The results of research were published in the scientific journal Molecular cell.
Prostate cancer: some details on the new research
“We took a closer look at a certain molecular machine called the spliceosome,” explains Anke Augspach, lead author of the study and researcher in the Department for Biomedical Research (DBMR). “It plays an important role in translating genes into proteins. In this process, the spliceosome separates the parts of the gene that are not needed for the production of the protein and fuses the other parts.
While almost all genes undergo this process in the so-called major spliceosome, the minor spliceosome is used in less than 1% of genes. “However, the minor spliceosome is enormously important because it specifically processes genes that play a crucial role in cell growth.
And it is this cell growth that gets out of control in cancer, but the precise mechanism behind this has remained unclear,” explains Rahul Kanadia. , co-author of the study from the Department of Physiology and Neurobiology and the Institute of Systems Genomics at the University of Connecticut
In their investigations, the team found various indications for the central role of the minor spliceosome in cancer. “We were able to show that a specific component of the minor spliceosome is significantly increased in advanced prostate cancer,” explains study co-author Mark Rubin from the Department of Biomedical Research (DBMR) and the Center for Precision Medicine (BCPM) Bern .
This has led researchers to suspect that cancer cells activate the minor spliceosome through this component and thus stimulate uncontrolled cell growth.
The researchers were able to confirm their hypothesis with the help of laboratory test models such as 2D cell cultures and organoids, miniature organs that are grown in the laboratory based on patient samples. They were also able to show that inhibition of the specific component led to a greater reduction in prostate cancer growth than current standard therapies.
“Consequently, blocking this process should hold therapeutic potential,” says Mark Rubin. “This is the lens we were looking for.” Rahul Kanadia adds that “the blockade leads to a decrease in cancer growth without affecting the growth and survival of normal cells.”
“This discovery is a game changer in the development of more effective and targeted combination therapies for cancers such as prostate cancer and other cancers. We want to work on this in the coming years and have already applied for the corresponding patent,” concludes Rubin.
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