Metastasis or Key to Beat Cancer

In recent decades there has been a steady increase in the number of cancer cases
worldwide. Among those patients, up to 20% of them develop metastatic forms of the
disease, which in solid tumours will eventually cause patients’ death. Therefore the
identification and implementation of more effective therapies to tackle this problem has
become a priority. Over the last decade significant efforts were undertaken to discover
target genes that can regulate the metastasis or act as markers throughout the process.
Several genetic signatures have been generated to divide the different types of cancer,
including the different subtypes of each of them. They are associated with a specific
clinical response. However the functional relevance of these genes and their role in
these signatures, with regard to the disease or the metastatic progression, still remain
unknown in general and particularly its potential therapeutic applications. Tumour
progression towards metastasis is often depicted as a multistage process in which
malignant cells spread from the tumour of origin to distant organs that will eventually
be colonized. However, these basic steps occur in the context of different organs,
emerge at different rates and are clinically managed in different ways depending on the
type of cancer. Therefore, we are currently faced with the challenge of incorporating the
biological heterogeneity of the clinical process into the research models of the
metastatic process.

Recent events indicate that the genes facilitating the process of metastasis are
functionally linked to the activation of both local stroma (within the tumour) and distant
stroma (e.g., bone), while facilitating tumour progression (Erler and Weaver, 2009). The
interaction with the environment, among others, can explain the metastatic ability of
different types of tumours to colonise the same or different organs (Fidler, 2003; Paget,
1889). This fact has aroused great interest in the scientific community to provide an
answer to this and to try to identify those genes favouring metastasis in specific organs
(Minn et al., 2007; Minn et al., 2005; Yin et al., 2003). Although it is unclear how
different tumours use these genes to do metastasis in the same organ.

In addition some tumours have a more restricted metastasis diffusion than others. For
instance, in the case of prostate cancer they are mostly restricted to the bone (Edlund et
al., 2004) and in the case of ocular melanoma are restricted to the liver (Triozzi et al.,
2008). A second key time in the metastatic process is its temporal evolution. In this way
breast and pulmonary endocrinomas usually colonise the same type of organs; for
instance, bone, lung, liver and brain (Hess et al., 2006). Nevertheless the temporal
process of metastasis between the two types of tumours is very different.

In the case of breast cancer metastatic events are observed after years or decades after
the primary event (Schmidt-Kittler et al., 2003). On the contrary in the case of
pulmonary cancer metastasis is observed shortly after diagnosis (Hoffman et al., 2000).
These clinical observations indicate that the fact of cancer cells infiltrate distant organs
is not always related to the fact of colonising them.