Metastasis: A Therapeutic Target for Cancer

Patricia S Steeg; Dan Theodorescu

Disclosures

Nat Clin Pract Oncol. 2008;5(4):206-219. 

In This Article

Summary and Introduction

Metastasis remains the major driver of mortality in patients with cancer. Our growing body of knowledge regarding this process provides the basis for the development of molecularly targeted therapeutics aimed at the tumor cell or its interaction with the host microenvironment. Here we discuss the similarity and differences between primary tumors and metastases, pathways controlling the colonization of a distant organ, and incorporation of antimetastatic therapies into clinical testing.

Despite years of therapeutic development and testing, mortality has improved only incrementally -- a few months at best, for many cancer types. Most patients with cancer succumb to metastatic disease or the complications of its treatment. These facts suggest the hypothesis that a mechanistic understanding of the metastatic process and the development of antimetastatic therapies may provide additional reductions in patient morbidity and mortality.

The metastatic process involves tumor cell invasion from the primary tumor, intravasation, arrest and extravasation of the circulatory system, followed by angiogenesis and growth at a distant site.[1,2] Metastatic progression is measured by the number and size of large lesions on imaging and by indices of patient survival.

Most of our data in cancer pertains to tumorigenesis. A minority of metastatic lesions is resected, so most histopathologic studies investigate primary tumor tissues. While many tumor cell lines were established from metastatic lesions, most fail to retain an in vivo metastatic phenotype upon prolonged culture. Furthermore, most drug development focuses on short-term changes in primary tumor size in preclinical rodent experiments. Is this a mistake? Is there evidence that the molecular wiring of a metastatic lesion is distinct from our commonly used tumorigenic lines and tissues?

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....