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.
- Luke R. Harrison, Dimitra Micha, Martin Brandenburg, Kathryn L. Simpson, Christopher J. Morrow, Olive Denneny, Cassandra Hodgkinson, Zaira Yunus, Clare Dempsey, Darren Roberts, Fiona Blackhall, Guy Makin, and Caroline Dive. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1. JCI, February 14, 2011 DOI: 10.1172/JCI43505
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