Inherited metastasis susceptibility and the implications for clinical prognosis

Extract: Metastasis, the spread of cancer throughout the body, remains the leading cause of cancer-related death despite decades of investigation and the efforts of thousands of doctors and scientists. Over the past thirty to forty years tremendous strides have been made in understanding the origins of cancer. Advances in new therapeutic agents and strategies have resulted in improved survival and cure rates in many cancers, particularly pediatric cancers. However, the presentation of a cancer patient with symptomatic metastatic disease continues to be a harbinger of poor outcome, given that secondary tumors are frequently both surgically untreatable and are frequently resistant to currently available anti-tumor drugs. To better battle this proximal cause of cancer mortality, a clearer understanding of the origins and mechanisms of the metastatic process are critical for the design of new clinical interventions. Metastasis is an extraordinarily complex process, and to successfully colonize a secondary site a cancer cell must complete a sequential series of steps before it becomes a clinically detectable tumor. These steps include separation from the primary tumor, invasion through surrounding tissues, entry into and survival in blood or lymph vessels, arresting in a distant site, usually followed by penetration into the surrounding tissue, survival in the distant organ site, proliferation, and creation of new blood vessels, all the while evading the immune response and intrinsic apoptosis mechanisms.