Genotoxic chemotherapy is one of the most common forms of cancer treatment. It is based on the use of drugs that kill cancer cells by inducing DNA damage. Most of these drugs, however, induce DNA damage also in healthy cells and, as a consequence, they evoke serious toxic effects limiting the therapeutic applications of these compounds.
Giulio Superti-Furga, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues port a way around this issue. The researchers discovered that YM155 (sepantronium bromide, pictured), a small antitumoral molecule under clinical trials, is a DNA damaging drug that is imported into cancer cells trough a transporter protein (SLC35F2). This feature renders YM155 a selective cytotoxic drug because its transporter is highly expressed in cancer cells and only less in healthy cells.
YM155 may represent a novel drug for genotoxic chemotherapy.
- The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity,
Georg E Winter, Branka Radic, Cristina Mayor-Ruiz, Vincent A Blomen, Claudia Trefzer, Richard K Kandasamy, Kilian V M Huber, Manuela Gridling, Doris Chen, Thorsten Klampfl, Robert Kralovics, Stefan Kubicek, Oscar Fernandez-Capetillo, Thijn R Brummelkamp, Giulio Superti-Furga,
Nature Chem. Biol. 2014.