Prostate cancer is essentially the most common non-skin cancer in men worldwide. Based on international estimates about one in six men will get prostate cancer during their lifetime and worldwide, over 375’000 patients will die from it annually. Tumor resistance to current therapies plays a necessary role on this and latest approaches are due to this fact urgently needed.

Now a world research team from the University of Bern, Inselspital Bern and the University of Connecticut (USA) has identified a previously unknown weak spot in prostate cancer cells. This weak spot is possibly also present in other cancer cells. The study was led by Mark Rubin from the Department for Biomedical Research (DBMR) and Center for Precision Medicine (BCPM) on the University of Bern and Inselspital Bern, and Rahul Kanadia from the Department of Physiology and Neurobiology and the Institute for Systems Genomics on the University of Connecticut. The research results have now been published within the journal Molecular Cell.

Previously unknown driver of prostate cancer identified

We took a better have a look at a certain molecular machine called the spliceosome. It plays a crucial role in the interpretation of genes into proteins. On this process, the spliceosome separates parts of the gene that will not be needed for the production of the protein and fuses the opposite parts.”

Anke Augspach, lead writer of the study and researcher from the Department for BioMedical Research (DBMR)

While just about all genes undergo this process within the so-called major spliceosome, the minor spliceosome is utilized in lower than one percent of genes. “Nevertheless, the minor spliceosome is enormously necessary since it particularly processes genes that play a vital role in cell growth. And it is that this cell growth that gets uncontrolled in cancer – however the precise mechanism behind this remained unclear”, explains Rahul Kanadia, study co-author from the Physiology and Neurobiology Department and the Institute for Systems Genomics on the University of Connecticut.

Of their investigations, the team found various indications for the central role of the minor spliceosome in cancer. “We were capable of show that a selected component of the minor spliceosome is significantly increased in advanced prostate cancer”, explains study co-author Mark Rubin of the Department for BioMedical Research (DBMR) and Bern Center for Precision Medicine (BCPM). This led the researchers to suspect that cancer cells activate the minor spliceosome through this component and thus stimulate uncontrolled cell growth.

A completely latest approach to cancer therapies

The researchers were able to verify their assumption with the assistance of laboratory test models comparable to 2D cell cultures and organoids – miniature organs which might be grown within the laboratory based on patient samples. They were also capable of show that inhibiting the particular component led to a greater reduction in the expansion of prostate cancer than current standard therapies. “Accordingly, blocking this process should hold therapeutic potential.”, Mark Rubin says. “That is the goal that that we were hunting”. Rahul Kanadia adds that “The blocking results in a decrease in cancer growthwithout affecting the expansion and survival of normal cells.” “This discovery is a game changer in developing simpler and targeted combination therapies for cancers comparable to prostate cancer and other varieties of cancer. We wish to work on this in the approaching years – and have already applied for the corresponding patent”, Rubin concludes.

Research supported with 1 million dollars

The research results come from a project supported by the US Prostate Cancer Foundation (PCF) with the Igor Tulchinsky-Leerom Segal-PCF Challenge Award 2022. The muse funds interdisciplinary projects that pursue promising approaches to combat recurrent or advanced prostate cancer. The award is endowed with 1 million dollars. “We commend the research team on their achievement and proudly support their work to bring us closer to our mission to eliminate death and affected by prostate cancer”, says Howard R. Soule, Executive Vice President and Chief Science Officer of the PCF.