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Established cancer cell lines play a central role in cancer cell
biology investigations and in the development of novel anticancer
treatments [ 13 , 14 ]. Their availability in large quantities and their
relative stable phenotypes/functional characteristics have obvious
advantages. Ability of anticancer agents to inhibit cell proliferation
or to induce cytotoxicity in human cancer cell line cultures has
been used in screening of novel anticancer compounds [ 15 ].
However, in vitro behavior of established cell lines poorly mirrors
in vivo cancer cell features. EAC cell lines established from primary
tumors are also widely used in the typical culture method of mono-
layer culture for screening of anticancer agents [ 3 , 15 – 17 ].
However, these monolayer culture models do not represent the
in vivo tumor microenvironment. There is considerable doubt
about the validity of cell culture models for drug development.
The major drawback of cell culture systems is that they are highly
artificial and do not represent human disease biology [ 18 ]. The
therapeutic resistance of EAC has been explored in a variety of cell
culture model systems with little clinical outcome. The subcutane-
ous xenograft model has been used extensively in esophageal can-
cer research and is generated by the transplanting of cultured cells
derived from human esophageal tumors in immunodeficient mice
[ 2 – 6 , 19 ]. These subcutaneous xenograft models are commonly
used for testing the efficacy of anticancer agents in many cancers
including EAC [ 2 , 3 , 5 – 9 ]. Because of the plentiful supply of cul-
tured human cancer cells, subcutaneous xenograft models are rela-
tively simple and less expensive to generate. Subcutaneous
xenografts have been extensively used in research in esophageal
adenocarcinoma, particularly for testing novel and new anticancer
agents [ 2 , 7 , 9 ]. They also provide an early assessment of potential
off-target and adverse effects of the new anticancer agents. Thus,
subcutaneous xenografts have many advantages and tumors are
easy to measure and have proven utility in predicting the clinical
activity of drugs [ 20 , 21 ]. Orthotopic models of esophageal ade-
nocarcinoma have been established by either implanting cancer
fragments or injecting cancer cells into the esophageal wall of the
mouse [ 10 , 11 , 22 ]. Orthotopic xenografts are believed to better
represent the tumor microenvironment that is associated with
human esophageal adenocarcinoma. Orthotopic models of esoph-
ageal adenocarcinoma also have several important limitations. Due
to the small size and location of the mouse esophagus, injecting
cancer cells or implanting tumor pieces into the esophageal wall is
technically challenging. On the other hand, mice subcutaneous
and orthotopic models of esophageal adenocarcinoma only repre-
sent local tumor growth and do not provide any information about
a survival benefit for a particular anticancer regimen, which is very
crucial for experimental treatment efficacy. In addition, it has been
observed that anticancer agents may well inhibit subcutaneous
tumor growth without effecting overall animal survival [ 21 ]. OneMd Sazzad Hassan and Urs von Holzen