Tumors and their microenvironments: tilling the soil. Commentary re: A. M. Scott et al., A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin. Cancer Res., 9: 1639-1647, 2003

Jonathan D Cheng, Louis M Weiner
2003 Clinical Cancer Research  
The conventional concept of tumor-host interactions is rooted in the realm of parasitology. A tumor invades an unsuspecting host, and in response to this assault, the host attempts to resist the advances of the tumor by calling on the armamentarium of the immune system. This implies a fundamental opposition between the tumor and host in purpose and intent. However, an accumulation of evidence points to an alternative paradigm, where the tumor microenvironment is not an idle bystander, but
more » ... ystander, but actively participates in tumor progression and metastasis (1, 2). In fact, stromal cells and their cytokines coordinate critical pathways that exert important roles in the ability of tumors to invade and metastasize (3). In this issue, Scott et al. (4) describe a Phase I clinical trial using the radiolabeled antibody sibrotuzumab to target the tumor stromal antigen FAP 2 in metastatic lung and colon cancers. Human FAP is unique in its selective expression by tumor stromal fibroblasts in epithelial carcinomas, but not by epithelial carcinoma cells, normal fibroblasts, or other normal tissues. Therefore, FAP is an attractive target for the study of tumor stromal cell biology and provides valuable insights into the roles of the tumor microenvironment. FAP may exemplify pathways by which the microenvironment soil is "tilled" in preparation for tumor invasion and metastasis.
pmid:12738710 fatcat:fpxlyydmnza7dhmxrfhuupsxc4