The team is focused on the design, synthesis, in vitro screening and in vivo testing of PUMA inhibitors as radioprotective agents in the anti-cancer therapy and for irradiated personnel exposed within radiation accidents or radiation terrorism.
Radiotherapy is one of the most important modalities in oncolgy. Its therapeutic potential is, however, limited by toxicity issues associated with irradiation of normal tissues. Both acute and chronic radiotoxicity have been associated with cell death. In radiosensitive tissues such as bone marrow or gastrointestinal tract, the cell death is predominantly mediated with programmed cell death - apoptosis. A pro-apoptotic protein PUMA plays a key role in this process. Thus, Inhibition of its functions increases resistance against radiation. Small molecule inhibitors of PUMA seem therefore very promising in respect to selective modulation of normal tissue damage. Such may also find its use as radioprotectors in radiation accidents or radiation terrorism.
Working group performs: