Liquid biopsies and CTC assays — the scientific progress continues

A paper in the British Journal of Cancer has offered further validation of the potential roles for liquid biopsies and circulating tumor cells (CTCs) in the management of aggressive forms of prostate cancer (and in related clinical trials).

The new paper by Punnoose et al. (which is available as a full text article), along with an associated media release from Epic Sciences (the developer of the particular type of CTC assay used in this study) are focused on the loss of expression of the tumor suppressor known as phosphate and tensin homolog (PTEN) and how that loss may affect the ability to identify patients who might be candidates for treatment with drugs that act as PI3K/AKT inhibitors in men with castration-resistant forms of prostate cancer (CRPC).

This is a complex scientific paper that we will not attempt to explain in any great detail. From the perspective of the majority of prostate cancer patients, the key points worth noting are as follows:

  • PTEN is a very important biochemical in the evolution of prostate cancer, and the loss of expression of the PTEN gene is associated with poor prognosis and several other factors.
  • Using the new CTC-based assay described in this paper allowed the authors to
    • Determine the PTEN status of individual patients
    • Determine the correlation between PTEN status of patients based on  CTCs and the PTEN status of tissue samples from archival and fresh, matched tumor specimens from the same patients
  • PTEN gene status detected in CTCs was concordant with PTEN status in

    • Matched fresh tissue from 32/38 patients (84 percent)
    • Matched archival tissue from 24/39 patients (62 percent)
  • In metastatic CRPC patients, PTEN loss in CTCs was associated with
    • Worse survival in univariate analysis (HR = 2.05; P = 0.01)
    • High lactate dehydrogenase (LDH) in metastatic CRPC patients.

The bottom line to all of this is that the CTC assay used in this study appears to be more sophisticated than earlier forms of CTC test and may have considerable value in

  • Identification of the presence or absence of particular mutations (like loss of expression of the PTEN gene) that affect prostate cancer progression over time
  • Identification of patients who may be candidates for treatment with new drugs that have been designed to act as PI3K/AKT inhibitors (see, for example, Table 1 in this paper by Edlind and Hsieh)/li>
  • Early identification of patients who are at high risk for progression and who may not be good candidates for other types of treatment with more traditional forms of therapy

The practical application of this new form of assay for CTC levels will take a while to work out in detail, and it is not yet clear whether CTC assays based on liquid biopsies are practical and clinically meaningful tests for the majority of men diagnosed with prostate cancer. What we do know from this paper is that we now have another example of our evolving ability to individualize treatment for late stage forms of prostate cancer.

2 Responses

  1. Is it possible to complete the next-to-last bullet point, following “e.g.,”?


  2. Sorry Fred. Thanks for bringing this to my attention, and see modification above.

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