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MenaINV rise and Mena11A fall the cancer cell transitions to a more metastatic
shape and behavior. These metastasis promoting behavior changes include increased
migratory behavior, changes in shape, loss of adhesion to neighboring cells, and up
to 100-fold greater sensitivity to the chemical attractant that lures metastatic cells to
blood vessels.
In 2013, MetaStat Inc signed two licensing agreements – one with the
Massachusetts Institute of Technology and the other with Montefi ore Medical
Center, Bronx, New York – for the use of alternatively spliced mRNA and Mena
protein isoform biomarkers for diagnosis, prognosis, as well as treatment of metas-
tases of solid epithelial cancers. This platform directly links a therapeutic to its
companion diagnostic based on the detection and targeting of alternatively spliced
oncogenes, which drive tumor progression and resistance, thereby offering a unique
opportunity for personalized treatment of cancer.
Detection and Destruction of CTCs with Nanoparticles
and X-Rays
Early detection and eradication of circulating tumor cells (CTCs) is important for
the management of cancer metastases. A technique for detection and killing of
CTCs has been described that uses magnetic and bismuth nanoparticles, X-ray fl uo-
rescence spectrometry, and X-rays (Hossain et al. 2012 ). Nanoparticles are modi-
fi ed with tumor targeting agents and conjugated with tumor cells through folate
receptors over-expressed on cancer cells. A micro-magnet is used to collect CTCs
suspended inside a fl owing medium that contains phosphate buffered saline or
whole blood. Characteristic X-ray emissions from collected bismuth nanoparticles,
upon excitation with collimated X-rays, are used to detect CTCs. Dose of primary
X-rays can be enhanced to kill the localized CTCs in vivo by radiation-induced
DNA damage, enabling personalized cancer management.
Monoclonal Antibodies for Combining Diagnosis
with Therapy of Cancer
Monoclonal antibodies (MAbs) can be used both for diagnosing and targeting can-
cer and some examples were given in Chap. 2. Two tests – Poteligeo Test IHC
(immunohistochemistry) and Poteligeo Test FCM (Kyowa Medex) – were approved
in Japan in 2012 as companion diagnostics for mogamulizumab (Kyowa Hakko
Kirin’s Poteligeo) injection, a therapeutic MAb for treatment of adult T cell leuke-
mia (ATL). Poteligeo binds to CCR4, which is expressed on the surface of ATL
cells, which are killed by MAb-dependent cell-mediated cytotoxicity. The compan-
ion diagnostic tests detect the presence of CCR4 expressed by ATL cells before
10 Personalized Therapy of Cancer