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Topic: Reviews of Recent Advances in Research and Treatment for
Gastroenterological Malignancies

Introduction to Volume 1 Issue 3 of Journal of Cancer Metastasis and
Treatment

Masayuki Watanabe
Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
Correspondence to: Dr. Masayuki Watanabe, Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for
Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. E-mail: masayuki.watanabe@jfcr.or.jp

It is a great honor for me to introduce the third issue of recent progress in the understanding of the molecular
the Journal of Cancer Metastasis and Treatment. This is mechanisms of Barrett’s esophagus and esophageal
a special issue focusing on recent advances in research adenocarcinoma.
and treatment for gastrointestinal (GI) malignancies. Chronic inﬂ ammation is known to induce carcinogenesis.
Cancers arising from the GI tract, including esophagus, Among GI cancers, adenocarcinoma arising from
stomach, colorectum, liver, gallbladder and pancreas, are
frequently observed all over the world. According to the Barrett’s esophagus, gastric cancer from chronic gastritis
global cancer statistics 2012, there were approximately due to Helicobacter pylori infection, and colitic cancer
407,000 newly diagnosed cases with GI cancers and from inﬂ ammatory bowel disease, are well known
304,000 deaths among them. They accounted for as tumors related to chronic inﬂ ammation. Ida et al.
[1]
29% and 37% of all cancers excluding non-melanoma summarize molecular mechanisms that link chronic
skin cancer respectively. Recent progress in molecular inﬂ ammation and GI cancers.
biological techniques facilitated the understanding of Cancer metastasis develops through multiple
the mechanism of cancer development and progression. steps, including invasion, vascular permeation,
This issue contains nine review articles concerning the circulation, arrest and extravasation, proliferation
topics which attract a lot of attention in the ﬁ eld of GI and angiogenesis. Epithelial-mesenchymal
malignancies. transition (EMT) is considered to be essential for

Epigenetic alterations regulate gene expression tumor invasion and metastasis. Okabe et al. review
through mechanisms other than changes in the DNA the mechanisms of EMT as well as molecules, which
sequence. DNA methylation abnormality, a major play important roles during EMT in GI cancers.
epigenetic process observed in many types of cancers, is Recent advances in technology enabled not only
characterized by global hypomethylation and site-speciﬁ c to detect circulating tumor cells (CTCs) but also to
CpG island hypermethylation. Shigaki et al. summarize elucidate the characteristics of CTCs. Iwatsuki et al.
the accumulated evidence for clinical application to summarize the recent advances in methodology for
use aberrant DNA methylation levels in GI cancers. detecting CTCs and discuss the implication of CTC
MicroRNAs (miRNAs), which are small non-coding analysis in clinical and translational research.
RNA molecules, also regulate gene expression at the Cancer stem cells have the abilities for self-renewal
post-transcriptional level and play important roles in and differentiation, and are responsible for cancer
modulating various biological processes. Some miRNAs metastasis and chemoresistance. Recently, it has
act as onco-miR through attenuating the expression been revealed that cancer cells can change their
of tumor suppressor genes, while others act as tumor characteristics reversibly from stem cells to non-stem
suppressor miR through suppressing the expression cells, under the genetic and epigenetic regulations as
of oncogenes. Owing to the stability in plasma as well well as the inﬂ uence of microenvironmental factors. On
as formalin-ﬁ xed parafﬁ n embedded samples, various the other hand, environmental factors such as chronic
miRNAs have been reported to be biomarkers in human inﬂ ammation, obesity, metabolism and nutrition have
cancers. Hiyoshi et al. document the utility of miRNAs been reported to inﬂ uence carcinogenesis and the
as novel diagnostic/prognostic tools as well as therapeutic progression of colorectal cancer. Izumi et al. document
targets in GI cancers. how microenvironmental factors affect maintaining
Adenocarcinoma of the esophagus or esophagogastric stem cell properties in colorectal cancer. In tumor
junction has dramatically increased in Western countries cells, genetic mutations and tumor microenvironment,
for several decades and recently an increasing trend is such as hypoxia, cause alterations in multiple signaling
also observed in Asian countries. Although Barrett’s pathways and then the altered signals affect cellular
esophagus is well known as a precursor of esophageal metabolism. The most famous metabolic phenotype
adenocarcinoma, the molecular mechanism has remained characteristics of cancer cells are the Warburg effect:
unclear until recently. Imamura et al. demonstrate ATP are generated through glycolysis instead of

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