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microenvironment were signifi cantly different from those in myoblast containing
matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher
extravasation rates of cancer cells into the myoblast-containing matrices compared
with untreated cells, suggesting a role for adenosine in reducing extravasation.
These results show the usefulness of microfl uidic 3D model as a drug screening
platform and a promising tool for investigating specifi c molecular pathways involved
in cancer biology, with potential applications to personalized medicine.
Personalized Management of Cancers of Various Organs
Personalized Management of Brain Tumors
Brain tumors can be benign or malignant, with the latter being more frequent. Most
of the discussion in this section is about glioblastoma multiforme (GBM), which is
the most malignant and most frequent brain tumor and is currently incurable with a
median survival of <2 years after diagnosis and treatment. Worldwide ~175,000
cases occur annually of which 17,000 are diagnosed in the US. Several innovative
treatments are being developed but the mainstays of conventional treatment are che-
motherapy and radiation. Chemotherapy gives inconsistent results in terms of pro-
longation of survival. GBM is a complex, heterogeneous disease, which makes it
unlikely that a uniform approach would be suitable for all patients. There is need for
the development of personalized treatment modalities to address the heterogeneity
of this complex tumor phenotype.
Aptamers for Selective Targeting of Tumor Initiating Cells in GBM
GBM displays cellular hierarchy with self-renewing tumor-initiating cells (TIC),
also known as cancer stem cells (CSCs), at the apex. Although the TIC hypothesis
remains controversial and the functional assays to defi ne the TIC phenotype are
evolving, it has been shown that TICs may contribute to angiogenesis, spread of
tumor, and resistance to therapy. However, identifi cation of TICs by use of biomark-
ers characterized in normal stem cells has an inherent limitation to selectively iden-
tify TICs. A study adopted Cell-Systematic Evolution of Ligands by Exponential
Enrichment (Cell-SELEX) to identify aptamers that specifi cally bind to TICs in
GBM but not to human neural stem cells (Kim et al. 2013 ). These aptamers select
and internalize into GBM cells that self-renew, proliferate, and initiate tumors. As
aptamers can be modifi ed to deliver payloads, aptamers may represent novel agents
that could selectively target or facilitate imaging of TICs, which may be important
for improving therapeutic outcomes in individual patients.
10 Personalized Therapy of Cancer