The biological evolution and metastasis of prostate cancer

A new research letter in the journal Nature has addressed issues related to the ways in which prostate cancer evolves over time from an initial, small, localized tumor to widespread, metastatic disease.

Gundem et al. describe how they were able to “read” all of the DNA from tumor samples isolated from 10 men with prostate cancer, and then use the resulting data to create a “family tree” showing how changes at the genetic level, associated with the gradual spread of the cancer, lead to new tumors, some of which become resistant to treatment.

This research is also discussed two media releases, which are the basis for two separate reports on the ScienceDaily web site.

The first of these media releases (issued by Cancer Research UK) is focused on how the research team was able to “read” the DNA from all the identifiable prostate cancer-related tumors in 10 patients and create maps or “family trees” of the genetic evolution of 10 specific cases of prostate cancer over time. The second media release (issued by Johns Hopkins Medicine) is focused on a different aspect of the study findings: the fact that an established metastatic site of prostate cancer tumor can itself metastasize to form further tumors (helping to explain how metastases actually spread out through the body over time). The equivalent reports on the ScienceDaily web site can be found here and here.

From a scientific perspective, this research is important and exciting. It further confirms what most scientifically knowledgeable researchers have long suspected:

  • That the genetic make-up of prostate cancer evolves over time in a specific individual.
  • That there are several different genetic aberrations that can initiate the development of prostate cancer.
  • That prostate cancer cells that break free from the initial tumor and spread over time share common genetic faults unique to the individual patient.
  • That metastasis is a repetitive process — from initial tumor to initial metastasis and potentially from each metastatic site to new metastases.

The potential long-term implications of this research, however, help us all to understand why finding actual cures for prostate cancer remain so elusive. Basically, each prostate cancer and its evolution is dependent on both the initial genetic flaw that causes initiation of the cancer and on each subsequent evolution of the cancer as it metastasizes throughout the body. Thus, if one isn’t able to treat an aggressive cancer effectively early on, that cancer will gradually evolve such that by the time metastatic disease is actually evident (e.g., with two or three evident metastatic tumors on a bone scan) there may actually be multiple different genetic subtypes of that cancer growing in the patient — and not all of those subtypes will necessarily respond well to any one particular type of therapy.

2 Responses

  1. I would like to thank and commend the 10 men (and their families) who donated their entire bodies after their prostate cancer deaths for this important research project. Thank you. Treating this disease is like playing the game of “Whack-a-Mole”.

  2. I think this also gives us a sobering assessment of how often treatment for oligometastatic disease and focal treatment of index lesions are likely to be successful. I also wonder how much cytoreduction/de-bulking really slows progression.

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