Selective Inhibitors of Genotoxic Stress Induced NFκB Pathway for Cancer Therapy

Many cancer therapies such as chemotherapeutics or irradiation induce cancer cell death through DNA damage and DNA double-strand break. In response to such genotoxic stress, cancer cells activate DNA damage response mechanisms leading to nuclear factor kappa B (NF-κB) activation via the IKK/NF-κB pathway which promotes cancer cell survival and is responsible for chemotherapy resistance. Thus, the IKK/NF-κB pathway represents an attractive drug target. However, IKK and NF-κB do have very diverse functions and general inhibition leads to blocking of beneficial effects and hence severe side effects.  Researchers of the Max Delbrück Centrum developed a new class of pathway-tailored small molecule inhibitors which interfere only with a stimulus-specific NF-κB activation, while leaving other modes of NF-κB activation intact.