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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-8-7
pubmed:abstractText
Metastasis is responsible for most cancer deaths. Therapeutic strategies to prevent development of metastases thus have potential to impact on cancer mortality. Development of these therapies requires a better understanding of the biology and molecular events of the metastatic process. Metastasis is usually defined, clinically and experimentally, by evidence of the endpoint of the process, that is, the presence of metastatic tumors. Endpoint assays are suitable for determining if a therapeutic approach is effective, but can provide little information on how a treatment works in vivo and what steps in metastasis are affected. We describe here two methodological advances in the study of metastasis as a process: in vivo videomicroscopy, which permits direct observation of steps in metastasis, and a "cell accounting" technique that permits quantification of the fate of cells over time. These procedures have provided new and unexpected insights into the biology of the metastatic process. Based on these insights, we consider which steps in the metastatic process are biologically and clinically most appropriate as therapeutic targets for development of anti-metastasis therapies. We conclude that the most promising stage of the metastasis process for therapeutic targeting is the growth phase, after cancer cells have arrested in the microcirculation in secondary sites and have completed extravasation. Earlier phases in the process are either biologically inappropriate or clinically inaccessible, except in specific cases (e.g., chemoprevention strategies). The role of "seed" and "soil" in determining organ-specific metastasis is also discussed. The metastatic growth phase fortunately is a clinically broad target, and any treatment that limits growth of metastases prior to their causing irreversible harm to the patient has the potential to be clinically useful. A variety of therapeutic approaches to target this phase are under active development, including inhibition of angiogenesis or signal transduction pathways needed to support the growth of metastatic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-230X
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-121
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10818678-Allantois, pubmed-meshheading:10818678-Animals, pubmed-meshheading:10818678-Antineoplastic Agents, pubmed-meshheading:10818678-Cell Adhesion, pubmed-meshheading:10818678-Cell Count, pubmed-meshheading:10818678-Cell Division, pubmed-meshheading:10818678-Cell Movement, pubmed-meshheading:10818678-Cell Survival, pubmed-meshheading:10818678-Chickens, pubmed-meshheading:10818678-Chorion, pubmed-meshheading:10818678-Drug Design, pubmed-meshheading:10818678-Humans, pubmed-meshheading:10818678-Liver Neoplasms, Experimental, pubmed-meshheading:10818678-Mice, pubmed-meshheading:10818678-Microcirculation, pubmed-meshheading:10818678-Microscopy, Video, pubmed-meshheading:10818678-Neoplasm Metastasis, pubmed-meshheading:10818678-Neoplasm Transplantation, pubmed-meshheading:10818678-Neoplastic Cells, Circulating, pubmed-meshheading:10818678-Neoplastic Stem Cells, pubmed-meshheading:10818678-Organ Specificity
pubmed:year
2000
pubmed:articleTitle
Clinical targets for anti-metastasis therapy.
pubmed:affiliation
Department of Oncology, University of Western Ontario, Canada. Ann.Chambers@lrcc.on.ca
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't