An international research team has discovered a principle that explains the metastasis of prostate cancer. When cancer develops in the prostate, several spatially mixed cancer cell clones are created that can invade the organs surrounding the prostate. However, only a dominant cell clone spreads systemically in the body and creates metastases. In addition, new subcellular clones are often created in metastases that are passed on to other metastases.
The researchers also discovered that the ways the disease spreads also vary between patients. The genetic drivers found in cancer cell clones likely differentiate which subclones spread throughout the body and which are limited to the prostate in each patient.
The study, led by Steven Bova, Professor of Cancer Pathology at Tampere University, and Professor David Wedge of the University of Oxford, was published in the prestigious Nature Communications Journal.
The study analyzed samples from ten men in the course of their prostate cancer from diagnosis to death from metastatic disease.
It was the first to combine genomic evolutionary analysis of local and metastatic prostate cancer, with which these evolutionary signals can be detected in the blood and cerebrospinal fluid, ie in the so-called fluid biopsy.
Among other things, the study found that analyzing circulating DNA in the blood of men with prostate cancer does not always detect metastatic cancer DNA. Whenever cancer DNA is found, the major cancer cell clones connecting the metastases are always detected, and subclones – which are only present in a subset of metastases – are detected variably. According to the researchers, using a fluid biopsy to monitor metastatic prostate cancer seems warranted, even if it does not always perfectly reflect what is in the patient’s body. Therefore, more research is needed to improve and extend these results.
Remarkably, the study showed that prostate cancer subclones that have not yet spread and are only present in the prostate were not detected in the patients’ blood. If this proves correct in larger studies, it could mean that the presence of circulating tumor DNA is self-diagnostic of metastatic prostate cancer.
Metastatic prostate cancer can spread to the brain and form subdural metastases. Analysis of the cerebrospinal fluid from men with metastatic prostate cancer should help determine which men have subdural metastases and which subclones are present. This can have therapeutic effects as the subclones may respond differently to therapy. “
Professor Steven Bova, Professor of Cancer Pathology, Tampere University
The study is based on a cohort study entitled “PELICAN Integrated Clinical-Molecular Autopsy Study of Fatal Metastatic Prostate Cancer” initiated by Professor Bova at Johns Hopkins University in 1994.
The study will be conducted on tissue and fluid biopsy samples and patient histories of 33 men with metastatic prostate cancer who agreed to donate their bodies for a research autopsy at the time of death. Bova has continued studying this cohort since moving to Tampere University in Finland in 2011.
Woodcock, DJ et al. (2020) Prostate Cancer Evolution from Primary Multi-Line Metastases to Single Line Metastases Affecting Fluid Biopsy. Nature communication. doi.org/10.1038/s41467-020-18843-5.