What's new on circulating tumor cells? A meeting report
Breast Cancer Research
What's new on circulating tumor cells? Ameetingreport
Evi S Lianidou 0
Dimitris Mavroudis
Georgia Sotiropoulou
Sophia Agelaki
Klaus Pantel
0 Department of Chemistry, University of Athens , 15771 Athens , Greece
Circulating tumor cells (CTCs) provide unique information for the management of cancer patients. The 7th International Symposium on Minimal Residual Cancer has focused on state of the art research, including exciting advances in understanding the biology of metastasis, CTCs and tumor dormancy. Particular emphasis was placed on the relationship of CTCs to cancer stem cells (CSCs) and the relevance of most recent findings for the development of new targeted therapies. CTCs were evaluated as promising tumor biomarkers and the design and results of the first clinical trials to determine their clinical utility were discussed together with state of the art technology platforms for CTC imaging, detection, quantification and molecular characterization. A liquid biopsy approach that can be used for prognostic and predictive purposes was proposed for the analysis of CTCs.
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Introduction
Current research on circulating tumor cells (CTCs)
present in the peripheral blood and disseminated tumor
cells (DTCs) present in bone marrow provides new
insight into the biology of tumor dormancy and tumor
cell dissemination and will open new avenues for the
early detection of metastatic spread and its successful
treatment [1]. The 7th International Symposium on
Minimal Residual Cancer, organized by Evi Lianidou,
Dimitris Mavroudis, and Klaus Pantel, was held in
Athens, Greece on 16 to 19 September 2009. The
symposium brought together 220 basic and clinical researchers
who presented cutting-edge research and had an
excellent opportunity to have stimulating intense discussions
on new technologies and clinical implications of CTC/
Biology of metastasis and tumor dormancy
Danny R Welch (University of Alabama, Birmingham, AL,
USA) presented a vivid account of metastasis suppressors,
and especially breast cancer metastasis suppressor 1
(BRMS1), which is significantly downregulated in
metastatic disease by epigenetic silencing [2] and coordinately
regulates expression of multiple metastasis-associated
microRNAs [3]. BRMS1 differentially attenuates cellular
responses to mitogenic signals at varying steps within the
same signaling cascade, and specific modulation of
signaling responses received from the microenvironment
may ultimately dictate which environments are permissive
or restrictive for tumor cell growth [3,4].
George Calin (MD Anderson Cancer Center, Houston,
TX, USA) described the roles of microRNAs as
metastasis activators or suppressors. His concept that the
same microRNAs could be involved in both the CSC
phenotype and the ability of specific cancer cells to give
rise to metastases represents a mechanistic link between
the initial and the final steps of tumorigenesis [5].
Jean-Paul Thiery (IMCB A STAR, Biopolis, Singapore)
illustrated how epithelial-mesenchymal transition (EMT)
can play a major role in local and distant dissemination of
carcinomas. Understanding of the molecular mechanisms
regulating EMT in solid tumors will provide new insights
into mechanisms of cancer progression, detection of
metastases, and development of effective and
mechanismbased agents for improved therapeutic intervention [6].
Philip Tsichlis (Tufts University, Boston, MA, USA)
highlighted how microRNAs differentially regulated by
Akt isoforms control EMT and stem cell renewal in
cancer cells. His data show that induction of EMT, stem
cell renewal, cell survival and proliferation is controlled
by microRNAs whose abundance depends on the balance
between Akt1 and Akt2 rather than on the overall activity
of Akt [7].
In a stimulating lecture Julio Aguirre-Ghiso (Mount
Sinai School of Medicine, New York, NY, USA) reported
on the roles of stress signaling and the microenvironment
as regulators of tumor cell dormancy. Interestingly,
dormancy of DTCs in the bone marrow may depend on
the activation of tumor growth factor-beta signaling and
p38 activation, p53 induction, and ERK inhibition in
DHEp3 cells, indicating that microenvironment-derived
signals that impinge on stress signaling pathways might
be sufficient to induce a protracted state of cellular tumor
dormancy [8].
Ann Chambers (University of Western Ontario, London,
Ontario, Canada) presented a stimulating update on
imaging of experimental cancer metastasis and tumor
dormancy recapitulated in a three-dimensional cell
culture system. Initiation of proliferation and maintenance
of metastatic growth by a subset of cells delivered to
secondary sites represent rate-limiting steps, but a larger
population of cells that remain in a dormant state appears
to be resistant to cytotoxic chemotherapy and retains
metastasis-forming potential [9].
Lisa M Coussens (University of California, San
Francisco, CA, USA) indicated that anti-tumor-acquired
immunity mediated by CD4+ T (...truncated)