Compounds shut down the pump protein that expels chemotherapeutic agents from the cell.
Scientists at Duquesne University and the Medical University of South Carolina report discovering novel compounds with antitumor activity that are also active on drug-resistant cancer cells.
Delphian Pharmaceuticals, a San Francisco biotech company, has licensed the Duquesne technology. The compounds, like paclitaxol and vincristine, disrupt the tubulin that forms structural supports in the cell necessary for cell extension, migration, and survival, according to the researchers.
Many tumors develop resistance to chemotherapeutic agents by producing protein pumps such as P-glycoprotein, which expels the anticancer compound. Thus, the level of the drug is reduced, and the cancer cell escapes. The Duquesne compounds, however, are not removed from the tumor cells.
Unexpectedly, the team also discovered that the Duquesne compounds restored the sensitivity of drug-resistant cancer cells to other anticancer agents by inactivating P-glycoprotein. Compounds with such dual actions, i.e. cytotoxicity and the ability to reverse drug resistance, are unusual, the investigators say.
The results are reported in the online version of the Journal of Medicinal Chemistry.