1. Targeted Sequencing of
Primary and Metastatic
CRC Tumors
Vermaat et al. ___________Page 688
In the era of DNA-guided
personalized cancer treatment,
prediction analysis on tissue that
matters is essential. In this study,
Vermaat and colleagues
comprehensively compared the
genetic constitution of 1,264 genes
involved in clinically relevant cancer-
associated signaling pathways and
processes in 21 patients with primary
colorectal adenocarcinomas (CRC)
and subsequent hepatic metastases
using targeted deep-sequencing on
formalin-fixed, paraffin-embedded
tissue. Differences in genetic variations
between primary CRC and hepatic
metastases in important pathways are
of such magnitude that an impact on
treatment outcome is realistic. This
indicates that genetic analysis of
metastasis may have more predictive
power when patients are selected for
specific treatment modalities.
Omental Adipose Stromal
Cells Promote Endometrial
Cancer
Klopp et al. _____________Page 771
Visceral obesity is associated with a
higher incidence and mortality in
several intra-abdominal cancers.
Klopp and colleagues proposed that
tumor-tropic stromal progenitor cells
in visceral fat may contribute to this
relationship. Adipose stromal cells
were isolated from the omentum, and
their effects on endometrial cancer
progression were evaluated with a
xenograft model simulating the
relationship of human tumors with
regional adipose tissue. Compared
with stromal cells from subcutaneous
adipose tissue, omental stromal cells
exhibited stronger stimulatory effects
on tumor vascularization,
proliferation, and growth. These
findings may explain the increased
risk and mortality of cancer in
patients with excess visceral adiposity.
Live-Attenuated Listeria
Vaccines for Advanced
Cancers
Le et al. ________________Page 858
Listeria monocytogenes (Lm)-based
vaccines naturally target dendritic
cells and stimulate both innate and
adaptive immunity. In preclinical
studies, the use of Lm vaccines
resulted in enhanced tumor-specific
immunity, delayed tumor growth,
and improved survival. Le and
colleagues report the results of
2 phase I clinical studies in patients
with advanced cancer testing the
ANZ-100 [a live-attenuated Lm strain
(Lm ΔactA/ΔinlB)] and CRS-207 (the
Lm ΔactA/ΔinlB strain engineered to
express human mesothelin). Lm was
well tolerated, with encouraging dose-
dependent evidence of immune
activation. These findings provide
valuable insight into the safety and
dosing of this approach that will
advance the further development of
Lm vaccines.
The Journal of Clinical and Translational Research www.aacrjournals.org593
Highlights
Clinical
Cancer
Research
February 1, 2012 • Volume 18 • Number 3 Selected Articles from This Issue
Specific Tumor Hypoxia Targeting by TH-302
Sun et al. __________________________________Page 758
TH-302 is a hypoxia-activated prodrug currently in clinical trials for the
treatment of cancer. Using multiple complementary lines of evidence,
Sun and colleagues demonstrate that TH-302 selectively targets the hypoxic
regions of human xenograft tumors. In addition, their results show the
potential utility of a hypoxia biomarker to guide the selection of patients for
TH-302 treatment. The strong correlation between the magnitude of tumor
hypoxia by pimonidazole staining and TH-302 efficacy serves as the basis for
clinical trials that include analysis of patient biopsies stained with
pimonidazole and a comparison with TH-302 efficacy.
Sun JD, Liu Q, Wang J, Ahluwalia D, Ferraro D, Wang Y, Duan J, Ammons WE, Curd JG, Matteucci MD, Hart CP. “Selective tumor
hypoxia targeting by hypoxia-activated prodrug TH-302 inhibits tumor growth in preclinical models of cancer” Clin Cancer Res 2012;
18: 758-770