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Cancer Of Unknown Primary Site.

G. Varadhachary, M. Raber
Published 2014 · Medicine

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Cancer of unknown primary site was once viewed almost as a separate type of cancer, with the assumption that, regardless of the site of origin, the tumors in unknown primary cancers shared biologic properties, perhaps including rapid progression and dissemination, which contributed to their presentation. This view drove the conduct of phase 2 empirical trials over the past three decades, with the goal of developing standard chemotherapy regimens that would be effective in all patients with unknown primary cancer. The underlying assumption was that varia- tions in presentation would not have a substantial effect on therapeutic approaches or survival. Our view of unknown primary cancer has evolved as our understanding of cancer biology in general has matured to become much more personalized. Many people now believe that tumors in unknown primary cancer may retain the signa- ture of the putative primary origin and that extending the management of known cancers to subtypes of unknown primary cancer can contribute to advancements in therapies for this disease. Cancer of unknown primary site could even be seen as the epitome of personalized medicine, with individualized treatment driven by the mutational status of each patient. The biologic events that allow the primary site to remain obscure after the development of metastases have not yet been defined. Studies that have shown chromosomal abnormalities, microvessel density, aneuploidy, and overexpression of several genes suggest that these abnormalities are not unique to unknown pri- mary cancer. 7-11 With the use of the Sequenom MassARRAY platform, a study involving consecutive patients with unknown primary cancer showed a low rate of mutations (in 18% of patients). 12 No new, low-frequency mutations were found with the use of a panel of mutations involving the phosphatidylinositol 3-kinase
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