Edinburgh Cancer Research UK Centre, Univeristy of Edinburgh, United Kingdom
Abstract:
Chemotherapy is the treatment of cancer with antineoplastic drugs, which commonly operate by killing cells that divide rapidly, one of the distinctive properties of cancer cells. Current treatments are however limited by lack of selectivity [1]. To mitigate unwanted side effects, many efforts have been made on the design of cancer-specific strategies such as prodrugs, which are derivatives of cytotoxic agents devoid of pharmacological activity that can be biochemically converted into its active form in a specific biological setting [1]. As a novel prodrug approach, our group is pioneering the use of a bioorthogonal organometallic (BOOM) activation strategy to develop spatially-controlled anticancer treatments. Bioorthogonal reactions are selective chemical processes that take place in biological systems, mediated by abiotic reagents, without interfering with the biotic components of the system [2, 3]. The use of bioorthogonal protecting groups that are selectively cleaved by metal catalysis allows to chemically “mask” the pharmacological activity of a drug to induce local activation by a catalyst-based “activating device”. Our group is investigating the use of Pd0-containing implants (the “activating device”) and the chemical modification of clinically-used anticancer drugs with Pd0-sensitive chemical groups to make “BOOM-activated prodrugs”. In this talk the seminal works published in this area [3, 4] and our last results will be presented.
REFERENCES:
[1] Rautio, et al. Nature Rev Drug Discov 2008, 7, 255-270.
[2] Prescher & Bertozzi. Nature Chem Biol 2005, 1, 13-21.
[3] Unciti-Broceta, et al. Nature Protocols 2012, 7, 1207-18.
[4] Yusop, Unciti-Broceta, et al. Nature Chem 2011, 3, 241-245.
