within particular cancers arises from different cell types
of which a tumor is comprised, as well as from genetic
and epigenetic factors that differ amongst the cancer
cells themselves. This gives rise to a disease that displays
a wide variety of phenotypes. In recent years, two theoretical
models (supported by experimental evidence) of cancer
growth and progression to a metastatic disease, have gained
prominence. These are (i) models of clonal evolution and
(ii) models based on the so-called cancer stem cell hypothesis.
In the former, microenvironmental selection pressures
are thought to drive mutations that generate clonal formations
best suited to the particular microenvironment and these
determine the tumor phenotype. In the latter theory, cancer
stem cells (CSCs) with similar genetic backgrounds can
be organized in a hierarchy corresponding to their tumorigenic
potential. Thus, CSCs appear at the top of the hierarchy
and are believed to drive the tumor initiating and metastatic
capabilities of the majority of cancers. A characteristic
feature of these types of models is the apparent unidirectional
nature of disease development and progression. In these
models, CSCs undergo symmetric division to replenish the
CSC pool, asymmetric division to produce one CSC and one
differentiated (non-CSC) daughter cell, or irreversible
symmetric division into daughter cells (non-CSCs) with
low tumorigenic potential. However, recent work from the
Weinberg group and others strongly points to yet another
possibility which supports a new model of tumorigenicity.
The experimental evidence suggests significant potential
plasticity that links the non-CSC and CSC compartments,
so that non-CSCs can reacquire a CSC phenotype and vice-versa.
Thus, under this CSC-Plasticity model, it appears that
some tumors may be driven by these bidirectional interchanges
which are common and essential components of its tumorigenicity.
There is mounting evidence implicating the plasticity
of cancer cells, in particular, as giving rise to aggressive
CSCs which are created anew within a tumor. There is much
current interest in clinical oncology on the therapeutic
targeting of CSCs, and this workshop will include talks
discussing not only clonal evolution, microenvironmental
selection pressures, CSCs, CSC-plasticity but also implications
for the development of future therapies.