The Ku complex is essential for DNA repair following double strand breaks following exposure to X-Rays. Potential inhibitors of this Ku complex could either block its interaction with the DNA backbone by binding as an anionic phosphate analogue or block formation of the required Ku70/Ku80 heterodimer for DNA repair. These inhibitors can be selectively targeted to cancer cells by conjugation to a macromolecule such as polyethylene glycol which should enter tumour cells via the EPR effect or monoclonal antibodies which bind biomarkers.
Could selective inhibition of this Ku complex within malignant tumours with subsequent exposure to X-Rays be an effective method of shrinking tumours or at least be a potential topic of research?
Reference;
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair,
John R. Walker1,2, Richard A. Corpina & Jonathan Goldberg, Nature 412, 607-614 (9 August 2001)