TITLE:
Correlation of an ex Vivo Model with Clinical Application of an Epigenetic Modifier, Inhibiting Tumor Growth and Metastasis, in Resistant Cholangiocarcinoma—A Case Study
AUTHORS:
M. A. Nezami, Aron Gould Simon, Geoffrey Bartholomeusz
KEYWORDS:
Cholangiocarcinoma, Epigenetic Therapies
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.1,
January
28,
2016
ABSTRACT: Bile duct cancer is a rare form of cancer, with approximately 2000 new cases
diagnosed in the United States each year. The prognosis of this disease is very
grave, especially in the form of intrahepatic (IHCC), as there is no person with
stage four who lives for 5 years, and the average prognosis is less than a year,
a majority of patients die in less than 6 months despite all therapies. It is suggested
that one of the key elements in the disease progression is the intratumoral hypoxia
inducible factor one alfa (HIF-1a) as a regulator of malignant behavior and recently
described as a new prognostic indicator of IHCC. (9, 10) HIF is a key regulator
under the microenvironmental (terrain) influence, and therefore studies of the cell
lines in an in vitro environment where
there is no hypoxia, usually fail to translate to a clinical outcome in vivo, unless the cells are transfected
by full-length HIF-1alpha (fL HIF-1alpha) and dominant-negative HIF-1alpha (dn HIF-1alpha).
To overcome this barrier, an ex vivo model
is designed at MD Anderson experimental therapeutics where the patient tumor sample
is transferred to the mice and treated with drugs, where the tumor can cross talk
with the actual terrain and mimic the human stroma where the HIF can be triggered.
Results show significant tumor necrosis on the intrahepatic cholangiocacinoma, only
after 5 days of exposure to an experimental compound that is known to suppress hypoxia-induced
accumulation of hypoxia-inducible factor-1α (HIF-1α) through inhibiting protein synthesis.
(11, 12) Further this is explored in the same actual patient with terminal diagnosis,
and proves itself with promising initial response. Here, we review this method and
the clinical perspectives, and suggest this method to be studied in larger trials.