What is a biomarker and how are CTCs defined as both a biomarker and as a carrier of biomarkers?

A biomarker is a short way of saying 'biological marker.' By definition, biomarkers are biological indicators of the existence of either a physiological (normal) or pathogenic (disease) process, or pharmacological response. Biomarkers include things like cells and proteins, and/or specific sequences of DNA, mRNA transcripts, non-coding RNAs.

The term biomarker has a different meaning in science as it does in medicine. In science, a biomarker is simple a signal of something - the thing that it is signifying can be normal or can be abmornmal. For instance, in experiments, scientists often use biomarkers as a way of simply telling that the experiment worked, like a means of control. In medicine however, the term biomarker most often has other meanings: the presence of a certain biomarker might for example signify a disease state. In can also refer to a substance that is introduced into the body to trace the function of a specific organ or function. A patient experiences symptoms, whereas a doctor will look for medical signs. Some of these signs may be in the form of biomarkers, for instance in a blood test, to help him/her identify what is going on. A biomarker might be as simple as a person's pulse or blood pressure, or as complex as something found through a blood test or biopsy.  Biomarkers may or may not correlate to a patient's sense of wellbeing.

And what does this have to do with Circulating Tumour Cells? Everything.

Here the terminology can get a little tricky: Circulating Tumour Cells (abbreviated as CTCs) are biomarkers, but they also contain biomarkers. CTCs were first found in patients over 100 years ago, but it has been only the last 10-15 years that they have become the focus of much clinical research and now they are a topic of great interest to Oncologists worldwide. The reason for this is three-fold, and has everything to do with the term biomarker.

Firstly, CTCs are understood and now widely accepted to be an independent prognostic biomarker. That is, the number of CTCs in the blood is associated with certain clinical endpoints - outcomes for the patient. There is one system, called CellSearch, that not only is the most studied system, but also has FDA approval for use in certain cancers. Technology moves quickly however, and there are now other methods with higher sensitivity and specificity that are fast become the focus of research.

Secondly, changes in CTC count over time is a biomarker of sensitivity or resistance to therapy. In other words, if the CTC count goes down after therapy and stays down, this can indicate that a therapy has been successful at targeting the cells that are responsible for cancer spread. This means that the patient is at less of a risk of developing metastases. Similarly, if the CTC count rises, this can indicate that the cells have developed a resistance to the therapy, and the patient is thus at increased risk of developing metastases. For this, the Maintrac test (Germany) has the greatest clinical validation.

Thirdly, CTCs are said to be a liquid biopsy - that is, their presence and information that they contain can be used to personalise cancer therapy. It is now very firmly acknowledged that no two cancers are identical. Because of this, CTC counting and analysis is an extremely valuable tool for practitioners. Practitioners are now utilising CTC testing to gain a greater understanding of the unique nature of a person's cancer.

Practitioners - there are two articles this week:

  1. The end of the beginning: Circulating Tumor Cells as a biomarker in castrate-resistant prostate cancer - American Society of Clinical Oncology 2014 - Download here
  2. Assessing the efficacy of targeted therapy using Circulating Epithelial Tumor Cells (CETCs): the example of SERM therapy monitoring as a unique tool to individualise therapy - J Cancer Research in Clinical Oncology 2010 - Download here