Finding the weak points may pave the way for more effective cancer treatments

Prostate cancer is the most common non-skin cancer in men worldwide. According to international estimates, one in six men will develop prostate cancer in their lifetime and more than 375,000 patients worldwide die each year. Resistance of tumors to current therapy plays an important role in this problem, so new approaches are urgently needed.

Now, an international research team from the University of Bern, Inselspital Bern and the University of Connecticut (USA) has identified a previously unknown weak point in prostate cancer cells. This weak point can also be present in other cancer cells. The research was led by Mark Rubin from the Department of Biomedical Research (DBMR) and Center for Precision Medicine (BCPM) at the University of Bern and Rahul Kanadia from the Department of Physiology and Neurobiology and the Institute for Systems Genomics. University of Connecticut. The results of the study are now published in the journal Molecular cell.

A previously unknown driver of prostate cancer has been identified

We took a closer look at a particular molecular machine spliceosome. It plays an important role in the conversion of genes into proteins. In this process, the spliceosome separates parts of the gene that are not needed for protein production and joins other parts together.”

Anke Augspach, lead author of the study and researcher at the Department of Biomedical Research (DBMR).

Almost all genes undergo this so-called process Major spliceosome, minor The spliceosome is used in less than one percent of genes. “However, the small spliceosome is very important because it specifically processes genes that play a key role in cell growth. In cancer, cell growth goes out of control, but the exact mechanism remains unknown,” explains Rahul Kanadia. , from the Department of Physiology and Neurobiology at the University of Connecticut and the Systems Genomics Institute, co-authored the study.

During the study, the team found various indications of 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 during advanced prostate cancer,” explains study co-author Mark Rubin of the Department of Biomedical Research (DBMR) and the Bern Center for Precision Medicine (BCPM). This led researchers to suspect that cancer cells activate the minor spliceosome through this component and thereby stimulate uncontrolled cell growth.

A completely new approach to cancer treatment

The researchers were able to confirm their prediction using laboratory test models such as organoids — miniature organs — grown in the lab based on 2D cell cultures and patient samples. They were also able to show that inhibiting a specific component significantly reduced the growth of prostate cancer compared to current standard therapy. “Accordingly, blocking this process should have therapeutic potential,” says Mark Rubin. “This is the target we are hunting.” Rahul Kanadia adds, “Blocking results in reduced 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 types of cancer. We want to work on this in the coming years and have applied for a corresponding patent,” concluded Rubin. .

The research was supported by 1 million dollars

The research results are from a project supported by the US Prostate Cancer Foundation (PCF) with the Igor Tulchinsky-Lerom Segal-PCF Challenge Award 2022. The Foundation funds interdisciplinary projects that pursue promising approaches to combating recurrent or advanced prostate cancer. The prize is 1 million dollars. “We applaud the research team for their achievement and are proud to support their work to bring us closer to our mission of ending the death and suffering of prostate cancer,” said Howard R. Soule, Executive Vice President and Chief Scientific Officer of PCF.


University of Connecticut

Journal definition:

Augspach, A. etc. (2023) Minor intron splicing is essential for survival in lethal prostate cancer. Molecular cell.

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