233target leading to longer retention times and the ability to deliver a higher payload of
the metal ion precisely to the target with a lower overall dose of the agent. The size
of these molecules leads to reduced immunogenicity and increased tumor penetra-
tion, further enhancing their effi cacy while minimizing potential side effects.
Combining Diagnosis and Therapy of Metastatic Cancer
Biomarkers of metastases of various cancers have been investigated. Examples are
given along with specifi c cancers. Examples are as follows:
CUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is
highly expressed in stem cells and frequently overexpressed and
tyrosine- phosphorylated in cancer. CDCP1 promotes cancer cell metastasis. A
study has shown that hypoxia induces CDCP1 expression and tyrosine phosphory-
lation in hypoxia-inducible factor (HIF)-2α–, but not HIF-1α–, dependent fashion
(Emerling et al. 2013 ). shRNA knockdown of CDCP1 impairs cancer cell migration
under hypoxic conditions, whereas overexpression of HIF-2α promotes the growth
of tumor xenografts in association with enhanced CDCP1 expression and tyrosine
phosphorylation. IHC analysis of tissue microarray samples from tumors of patients
with clear cell renal cell carcinoma shows that increased CDCP1 expression corre-
lates with decreased overall survival. Together, these data support a critical role for
CDCP1 as a unique HIF-2α target gene involved in the regulation of cancer metas-
tasis, and suggest that CDCP1 is a biomarker and potential therapeutic target for
metastatic cancers.
Mena protein potentiates and modulates cellular migration and is found in the
developing embryo where it plays an important role in the developing nervous sys-
tem among other functions. It facilitates and organizes formation, extension and
navigation of growing nerve fi bers through tissue to link with other neurons, form-
ing the proper circuits needed for a functional nervous system. However, in meta-
static cancer cells, high levels of the Mena protein accumulate and infl uence a
number of intracellular signaling programs. Mena facilitates a process whereby
tumor cells send out a well-organized protuberance that invades surrounding tissue
and pulls the remainder of the cell behind it. Mena modulates the strength and direc-
tion of this invasive process and steers the migrating cancer cell in the direction of
blood vessels through its ability to modulate the metastatic cell’s response to chemi-
cal signals that attract it to blood vessels. Mena is present in cancer cells in several
isoforms that are similar but slightly different in structure. Despite similarity in
structure, protein isoforms differ considerably in their infl uence on cells. MetaStat
Inc has identifi ed the most dangerous isoform of Mena named MenaINV (Mena
invasive). Mena11A, on the other hand, is the Mena isoform that seems to exert a
much more positive infl uence on the cell’s behavior, reducing the ability of cells to
break away from the tumor and invade and migrate toward blood vessels. Metastat’s
key discovery is that it can predict the metastatic potential of a cancer cell by mea-
suring the relative levels of MenaINV and Mena11A. As the relative levels of
Molecular Diagnostics Combined with Cancer Therapeutics