Evolution of the Development of PARP Inhibitors.

ABSTRACT

PARP inhibitors first entered the clinic in 2003 in combination with DNA damaging agents in an attempt to overcome treatment resistance to established agents. A brief overview of ADP-ribosylator enzyme biology and the early preclinical development of the class is discussed, illustrating the multiple biological activities of these enzymes and potential wider clinical applicability. The chapter then documents those early years of clinical development and the evolution of the field and eventual registration of PARP inhibitors as active anticancer agents in their own right-in genetically vulnerable tumours.