What's new on circulating tumor cells? A meeting report

Breast Cancer Research, Jul 2010

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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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. - 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)


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Evi S Lianidou, Dimitris Mavroudis, Georgia Sotiropoulou, Sophia Agelaki, Klaus Pantel. What's new on circulating tumor cells? A meeting report, Breast Cancer Research, 2010, pp. 307, 12, DOI: 10.1186/bcr2601