Genes and metastasis: experimental advances and clinical implications

Abstract

Metastasis is the spread of cancer from a primary site resulting in the establishment of secondary tumors in distant locations. It is often difficult to determine if the metastatic process has begun at the time of removal of a primary tumor, creating uncertainty in patients with regards to possible cancer recurrence. Moreover, the majority of cancer deaths occur due to the physiological effects of metastasis rather than from the consequences of the primary tumor. The identification and characterization of molecular factors which contribute to metastasis therefore provides the potential for developing novel prognostic and/or therapeutic strategies to combat cancer mortality. The development of metastasis requires the coordinated expression and function of many different genes. Dysregulation of the balance between the expression of genes which promote metastasis and those which suppress metastasis can influence a cell’s ability to successfully complete all the steps in the metastatic cascade. In this chapter, we summarize what is known about the metastatic process and discuss some of the many studies which have investigated different classes of molecules known to be associated with and/or contribute to metastasis. These factors include oncogenic proteins, growth and angiogenic factors, cellular receptors, factors important for cell attachment, enzymes which degrade the extracellular matrix, molecules important for intracellular signalling, chemoattractant molecules, and factors associated with gene transcription. We also consider the emerging role of DNA microarray technology in helping to define the relationship between genes and metastasis both within and between different tumor types. Finally, we discuss how this evolving knowledge about metastasis-associated genes can be translated into clinical strategies for the management, treatment, and cure of metastatic disease.