New Vulnerability in Prostate Cancer Cells Uncovered

In an international scientific endeavor, a previously unknown weakness in prostate cancer cells has been identified. This weakness involves an element of the minor spliceosome, which experiences significant elevation in advanced prostate cancer and prompts uncontrolled cell growth. The scientists found that halting this component resulted in a major decrease in the growth of prostate cancer compared to traditional treatments, promising more efficient, directed therapies that could be potentially relevant to other cancer types.

Prostate cancer is the most common non-skin cancer among men worldwide. Estimates indicate that one in every six men will be diagnosed with prostate cancer in their lifetime, with yearly fatalities surpassing 375,000 patients.

Contributing to these alarming statistics is the inherent resilience of cancer cells to existing treatments, underlining the immediate need for new therapeutic approaches. In a revolutionary breakthrough, an international collaborative research effort involving the University of Bern, Inselspital Bern, and the University of Connecticut (USA) has unearthed a previously unseen vulnerability in prostate cancer cells. This weakness could also exist in other types of cancer cells.

The study was guided by Mark Rubin of the Department for Biomedical Research (DBMR) and Center for Precision Medicine (BCPM) at the University of Bern and Inselspital Bern, and Rahul Kanadia of the Department of Physiology and Neurobiology and the Institute for Systems Genomics at the University of Connecticut. The research findings have been published in the journal Molecular Cell.

New Culprit behind Prostate Cancer Revealed

Anke Augspach, lead author and DBMR researcher, explains, “We inspected a molecular mechanism known as the spliceosome. It’s crucial in the conversion of genes into proteins by eliminating unnecessary gene segments and merging the remaining ones.”

While the major spliceosome processes almost all genes, the minor spliceosome handles less than one percent. “However, the minor spliceosome is of great importance because it primarily deals with genes that significantly influence cell growth. It’s this cell growth that becomes unmanageable in cancer, but the exact mechanism remained elusive,” adds Rahul Kanadia from the University of Connecticut.

Through their research, the team pinpointed numerous signs of the minor spliceosome’s critical role in cancer. “We demonstrated that a specific element of the minor spliceosome sees a significant increase in advanced prostate cancer,” says study co-author Mark Rubin from DBMR and BCPM. This observation led the researchers to hypothesize that cancer cells stimulate the minor spliceosome, driving uncontrolled cell growth.

Pioneering Method to Cancer Treatment

The researchers were able to validate their theory using lab models such as 2D cell cultures and organoids – miniature organs grown in labs from patient samples. They found that halting the specific element led to a larger reduction in prostate cancer growth than conventional treatments.

“This process, if blocked, could possess therapeutic potential,” Mark Rubin comments. “That was the target we were searching for.”

Rahul Kanadia adds that “the blocking results in a decrease in cancer growth without compromising the growth and survival of normal cells.”

“This breakthrough could revolutionize the development of more effective and targeted combination therapies for cancers like prostate cancer and potentially other types. We intend to further our work on this in the coming years and have already filed for the relevant patent,” Rubin concludes.

The research findings come from a project backed by the US Prostate Cancer Foundation (PCF) through the Igor Tulchinsky-Leerom Segal-PCF Challenge Award 2022. The foundation supports interdisciplinary projects that seek innovative methods to fight recurrent or advanced prostate cancer, with the award being endowed with 1 million dollars. Howard R. Soule, PCF’s Executive Vice President and Chief Science Officer, commends the research team on their achievement and reaffirms the foundation’s support for their work to eliminate death and suffering from prostate cancer.

Reference: “Minor intron splicing is critical for survival of lethal prostate cancer” by Anke Augspach, et al, 8 June 2023, Molecular Cell. DOI: 10.1016/j.molcel.2023.05.017

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More about Prostate Cancer Vulnerability

• University of Bern
• Inselspital Bern
• University of Connecticut
• US Prostate Cancer Foundation
• Original Research Paper in Molecular Cell
• Information on Prostate Cancer