Molecular correlates of site-specific metastasis

Metastasis is the spread of tumor cells from a primary site to distant organs. It is the major cause of cancer morbidity and death. In the last few decades, significant advances have been made in surgical techniques, radiation therapy delivery, and chemotherapy including the development of combination regimens and agents inhibiting newly characterized biological targets. Treatment of metastasis, however, remains the most challenging task in cancer therapy because metastatic growth relies on complex interactions between tumor cells and the host and is often resistant to all therapeutic modalities. Management of metastasis in bone is especially challenging given the difficulty of access for therapeutic agents. Contemporary research seeks to explain the striking organ specificity observed in metastasis. In this article, we will examine historic perspectives on site-specific metastasis and review cellular and molecular evidence pertinent to the mechanisms of organ specificity. We will discuss a number of studies that aim to identify gene signatures correlating with organ-selective metastasis using microarray technology. Lastly, we will discuss potential areas of future research including microRNAs, proteomics, and the development of diagnostic and therapeutic interventions.