Dissecting Metastatic Disease: The Paradigm of Cancer of Unknown Primary Origin

A fundamental axiom in cancer research describes tumorigenesis as a multistep process in which genetic events that activate oncogenes or inactivate tumor suppressor genes are sequentially acquired, frequently in a genetically unstable background. Despite this theoretical concern, experimental evidence and clinical examples have shown that the multistage process of carcinogenesis is not a simplistic sum of effects deriving from activated oncogenes or inactivated tumor suppressor genes, but is a more complex scenario. Growing evidence suggests that dissemination of primary cancer cells to distant sites might be an early event. Indeed, early metastatic cancers define aggressive and difficult-to-treat diseases. In some cases, the metastatic phenotype even prevails on the growth of the
primary neoplastic mass in absence of clearly referable lineage of origin. The later is known as Cancer of Unknown Primary (CUP) and represent an intriguing and paradigmatic model of the biological process that drives a hyper-aggressive malignant phenotype.

We welcome manuscripts addressing the following themes:

• Genetic basis of CUPs and early metastatic cancers
• Pathological issues and definition of metastatic disease
• Metastatic dissemination in immunocompromised patients
• Mathematical and physical dynamics of metastatic spreading
• Clinical management of CUPs and early metastatic cancers
• Clinical and molecular epidemiology of CUPs
• Lineage evolution and tracking of metastatic spreading