Researchers Discover Molecular Steps that Drive Aggressive Growth in Prostate Cancer


Prostate cancers often become more aggressive and resistant to treatment as they grow and spread in the human body. Among these aggressive tumors is a rare and treatment-resistant type called small cell neuroendocrine (SCN) cancer. For the first time, researchers have documented the molecular steps that transform a more common type of prostate cancer into SCN cancer, providing valuable insights for the development of new therapies to prevent SCN prostate cancers.

The research was conducted by Dr. Owen Witte and Thomas Graeber, both members of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and Jonsson Comprehensive Cancer Center. Dr. Witte states, “For the first time, we have a real opportunity to define the process that leads these very, very aggressive tumors.”

While SCN cancers make up a small percentage of newly diagnosed prostate cancers, they are more prevalent among tumors that continue to grow after treatment. SCN prostate cancers are known for their fast growth and resistance to treatment. Although the molecular differences between common prostate adenocarcinomas and SCN cancers have been identified, the research has yet to unveil the specific mechanisms behind these changes.

According to the study published in Cancer Cell, the researchers used a model of prostate cancer in mice, where healthy human prostate cells were implanted and manipulated to develop into adenocarcinomas and subsequently SCN cancers. This unique model allowed the researchers to track the progression and identify molecular changes at each stage.

Over the course of 10 weeks, the researchers collected biopsies every two weeks and analyzed the genetic programs that were activated. Surprisingly, despite the numerous differences between prostate adenocarcinomas and SCN cancers, there were only two discernible pathways through which prostate adenocarcinomas evolved into SCN cancers. Additionally, the team found that certain lung cancers followed similar paths of progression towards SCN cancers.

Dr. Graeber explains, “It was a real surprise that there were just two major pathways… it gives us a lot of hope for therapeutics, because it’s much easier to figure out how to block two paths than hundreds.”

The researchers plan to conduct further studies to develop methods to block these newly discovered pathways. Many of the identified molecular changes could potentially be targeted with drugs. Rather than developing drugs to treat full-blown SCN prostate or lung cancers, the researchers propose using drugs to halt the progression of less aggressive subtypes, thereby preventing the development of SCN cancers.

Dr. Witte emphasizes the importance of their findings, stating, “This is a reproducible process that cancers take to become more aggressive, and if we can predict that a cancer is headed down that road, maybe we can prevent it.”

This groundbreaking research sheds light on the mechanisms that drive the aggressive growth of prostate cancer and opens up new possibilities for the development of preventative and more effective treatment strategies.



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