Biomedical Engineering Reference
In-Depth Information
Fig. 2 Model of the mCSC-mediated metastatic cascade. An initial oncogenic event gives rise
to a pCSC capable of proliferating to induce a tumor (a). Depending on the inherent meta-
static characteristics of the pCSCs, signals such as VEGF and PlGF are secreted into the
systemic circulation to prime and remodel pre-metastatic niches (b). Factors released from the
pre-metastasis niche can signal back to tumor cells to promoter invasion and metastasis (c).
mCSCs migrate into the circulation and home in on target organs with appropriate niches (d).
Once anchored to the secondary site the mCSC may enter a quiescent state (micrometastasis)
until activating signals in the environment induce it to begin proliferation and drive formation
of a metastatic tumor (e)
6 mCSCs: Novel Opportunities for Therapeutic Intervention
Understanding the role of mCSCs in cancer progression and fatality will open
many new opportunities for clinical intervention which may better target the
source of metastatic growth. If CSCs truly are the root of malignancy and solely
responsible for tumor growth, only therapies that deplete this population will
ultimately be successful as an effective cure. A greater understanding of CSCs is
still needed to develop therapeutics directly targeting them, but progress is
being made in this direction.
Current standard treatment for most cancers involves some combination of
chemotherapy, hormonal therapy, radiation treatment, as well as a growing list
of molecular targeting therapeutics, depending on tumor characteristics and
stage. Following treatment, tumor regression is normally used as an indicator of
therapeutic success. In order to better treat cancer, new ideas about CSCs must
be integrated into our understanding of clinical intervention. Both standard
treatment and current diagnostic end points are likely not applicable to the CSC
