thesis
Circulation Tumor Cells: counts and characteristics
- Publication date
- 21 September 2012
- Publisher
- In recent years, many new anti-cancer agents have been developed and introduced into
clinical care. While these new agents have led to substantial gains in response rates and
life expectancies, they have also increased the need for tools to select those patients
benefitting from said therapies. Once patients develop metastatic disease, treatment is aimed
at improving quality of life and prolonging life expectancy, but is always a trade-off against
the side-effects that are inevitably associated with anti-tumor therapy, underscoring the need
to select only those patients who are likely to respond to a particular drug. However, there is
still an unmet need for such an array of reliable predictive factors, a need that can be met by
designing studies in which patient subgroups are defined and stratified based on rational,
biology-driven but feasible tumor characteristics. An increasing number of studies is being
designed in which, for example, only patients with a specific gain-of-function mutation are
subjected to a monoclonal antibody therapy aimed at the activated pathway this gene is
involved in. While substantial progress is being made with this approach, patient selection
has thus far been far from perfect. Even a powerful predictor such as a KRAS mutation for
EGFR-inhibiting therapy results in a response in just 20% of patients who are deemed
sensitive based on their KRAS wild-type status. One of the reasons for the disappointing
performance of predictive factors could be the fact that they are most often based on
primary tumor characteristics, while at the time of metastatic disease, a patients’ prognosis is
determined by their metastatic tumor load and its biological phenotype. Through processes
such as clonal selection and the inherent genomic instability of the tumor or as a consequence
of therapy pressure, metastatic tumor cells can differ substantially and vitally from primary
tumor cells. Analysis of metastatic tissue would thus probably be better indicative of
the actual tumor load and its underlying biology, and lead to better response prediction.
Unfortunately, repetitive metastatic biopsies are invasive and painful, understandably limiting
their use in clinical practice. Circulating tumor cells (CTCs) provide a very promising solution
for this problem, as they can be obtained and characterized repetitively and non-invasively
through venipunctures, and thus serve as a surrogate ‘liquid biopsy’ of metastases.