Most, if not all, solid tumors contain regions that are not well oxygenated. Tumor cells in these regions, which are known as hypoxic regions, are usually resistant to the death-inducing effects of chemotherapeutics. But now, Caroline Dive and colleagues, at Manchester University, United Kingdom, have identified a compound (ABT-737) that induces human cancer cells exposed to hypoxic conditions in vitro to undergo a form of cell death known as apoptosis. In addition, cells in hypoxic regions of human tumors xenografted in mice were susceptible to ABT-737–induced apoptotic cell death. As ABT-737 synergized with conventional chemotherapeutic agents in tumor-bearing mice, the authors suggest that such a combination of drugs could improve treatment of solid tumors.
TITLE: Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1
AUTHOR CONTACT:
Caroline Dive
Paterson Institute for Cancer Research, Manchester, United Kingdom.
Phone: 00.44.161.446.3036; Fax: 00.44.161.446.3109; E-mail: cdive@picr.man.ac.uk.
View this article at: http://www.jci.org/articles/view/43505?key=b39a1fa8ed3af3fab6a0
Journal
Journal of Clinical Investigation