Question ID: Feb 2-1
Submitted by: February 2, 2011 Clinical and Translational Sciences Provocative Questions Workshop - Submitted to the website
March 3, 2011
What is the clinical significance of finding cells from a primary tumor at another site?
Background: Metastatic disease is known to be the major cause of death from cancer. But, just as not all primary cancers are prone to metastasize, not all tumor cells found at secondary sites are life-threatening. Dissemination from a primary growth can occur relatively early in tumor development, and cells at secondary sites may have properties that range from dormancy to aggressive malignancy. Furthermore, relatively quiescent tumor cells may require additional genetic and/or epigenetic alterations, perhaps in conjunction with non-cell autonomous alterations, to achieve a fully malignant phenotype at the secondary site. Yet, because the spread of tumor cells is usually viewed as an unfavorable prognostic indicator, detection of such cells commonly represents the main rationale for more intensive therapy, which may or may not be warranted. For example, in some cancers (testicular, bladder), removal of lymph nodes with disseminated cells is helpful, but in others (breast, melanoma) it has no impact on outcomes.
Feasibility: New experimental methods, including capture of circulating tumor cells, sensitive techniques for detecting and characterizing small numbers of tumor cells at secondary sites, and the development of improved animal models of cancer, have created opportunities for expanding our knowledge of disseminated cells and refining our lexicon for classifying them. For instance, recent advances in DNA sequencing enable the generation of phylogenetic trees of tumor cell populations to determine their clonal relationships and evolutionary distance from each other and from portions of the primary tumor that are at different stages of progression. With these new tools, it may now be possible to establish the points in tumor progression when cells escape from the primary tumor; define the malignant potential of disseminated cells; and identify non-cell autonomous factors and autonomous genomic events that convert dormant cells into aggressively malignant cells.
Implications of success: Such analyses could enhance our understanding of the mechanisms that account for a lack of oncogenicity of tumor cells at a secondary site and the mechanisms that contribute to their malignant behavior at those sites, as well as improve our ability to predict the biological behavior tumor cells found at those sites. This information would give clinicians a clearer picture of when intervention is needed to treat such tumor cells and which can safely be left alone or followed for potential later action. A better understanding of the timing of tumor cell dissemination, biological relevance of those cells, and the progressive transformation of disseminated cells, could improve cancer staging, reduce morbidity and associated health care costs from unnecessary cancer treatment, and define drug targets in a variety of disseminated cell types.
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