Researchers have achieved a groundbreaking milestone by meticulously documenting the molecular transformations that convert a common form of prostate cancer into a rare and treatment-resistant small cell neuroendocrine (SCN) cancer. This revelation opens new avenues for understanding tumor evolution, potentially leading to innovative therapies to impede the development of SCN prostate cancers.
Dr. Owen Witte and Thomas Graeber, co-leaders of the research from the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, alongside the Jonsson Comprehensive Cancer Center, emphasize the significance of defining the process behind these highly aggressive tumors. While SCN cancers constitute a small percentage of newly diagnosed prostate cancers, they are more prevalent in tumors that persist after treatment, exhibiting rapid growth and resistance to treatment.
Although molecular distinctions between common prostate adenocarcinomas and SCN cancers were previously identified, the mechanism triggering these changes remained elusive. The research, published in Cancer Cell, employed a prostate cancer model where healthy human prostate cells, when implanted into mice, were manipulated to progress from adenocarcinomas to SCN cancers.
Tracking the progression over 10 weeks through biopsies and genetic analyses, the researchers uncovered that prostate adenocarcinomas primarily follow two distinct paths to evolve into SCN cancers. The unexpected simplicity of only two major pathways provides hope for therapeutic interventions, as understanding and blocking a limited number of routes is more manageable than tackling numerous possibilities.
The researchers plan to conduct further studies aimed at developing strategies to inhibit these identified pathways. Certain molecular changes critical for SCN cancer evolution could be potential targets for drug interventions. Instead of the formidable task of creating drugs for advanced SCN prostate or lung cancers, the researchers propose focusing on preventing the progression of less aggressive subtypes to curb the emergence of SCN cancers.
In essence, this study underscores a reproducible process that cancers undergo to become more aggressive. The hope lies in predicting the trajectory towards aggressive cancer, allowing for preventive measures. The prospect of intervening before the full-blown development of SCN cancers presents a promising strategy for managing and potentially thwarting their progression.