A possible future test to differentiate between risk for aggressive and indolent forms of prostate cancer

A new paper by an  international group of researchers from several different centers has maybe identified a new way to differentiate accurately between indolent and aggressive forms of prostate cancer at time of initial diagnosis.

This new paper by Labbé et al. is based on data from > 2,500 very well-characterized patients with aggressive forms of prostate cancer. What Labbé et al. have been able to show is the following:

  • Simultaneous (the authors use the term “concurrent”) expression of two specific genes (the so-called TOP2A and EZH2 genes) in prostate cancer tissue is highly associated with the presence of aggressive forms of prostate cancer.

Basically, what the authors did was to use tissue specimens and related data from multiple groups of patients with advanced forms of prostate cancer to show that the concurrent presence of TOP2A mRNA, EZH2 mRNA, and up-regulation of associated proteins could identify a subgroup of primary and metastatic prostate cancer patients with more aggressive disease and notable overlap of genes involved in the regulation of cancer cell growth (mitotis).

They also used immunohistochemical staining to test for the presence of TOP2A and EZH2 in a small group of 89 men with primary (i.e., initially localized) prostate cancer whose outcomes were known over time.

Thirdly, they investigated the therapeutic potential of a combination therapy (probably docetaxel + ADT) in targeting both TOP2A and EZH2 using prostate cancer developed in mouse cell lines in the laboratory.

Now this is all early stage research, and it will need to be confirmed in larger sets of early stage patients, but if it could be shown that there is a really strong association between the expression of these two genes and the development and presence of more advanced (i.e., progressive and metastatic) forms of prostate cancer, this might allow us to do two things much better:

  • Identify men with aggressive forms of prostate cancer with accuracy much sooner (which might be extremely important in the identification of patients at lower and higher levels of risk who had been diagnosed with a Gleason score of 7)
  • Monitor men on active surveillance over time with a higher degree of accuracy in terms of their risk for progressive disease

However, one thing that your sitemaster does want to be very clear about is that this type of data is not going to lead to the availability of some marvelous new test a couple of years from now. It might take 5 or more years to get to the point at which we know exactly how accurate such a test might be and whether it could be carried out using a blood sample or only given the availability of a prostate cancer tissue sample. Clearly, the former would be the ideal.

One Response

  1. I find it frustrating how uninformative the abstract is! Among things we’d certainly like to know are: (1) how prevalent the concurrent up-regulation of these two genes is in aggressive prostate cancer; (2) what was the combination therapy (I see no reason to assume it was docetaxel + ADT); and (3) was it administered in vitro or in vivo?

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