Grant: Project Grant

It has been known for decades that the presence of cells with little or no oxygen causes resistance to both radiotherapy and chemotherapy. These 'hypoxic' cells result from the proliferation of cancer cells beyond the ability of the blood vessels to supply oxygen. Radiotherapy and many chemotherapy agents owe their activity to DNA damage. This damage is reduced in hypoxic cells compared to oxygenated cells and so cancer cells survive and result in tumour regrowth.¿We have synthesized inhibitors of DNA damage repair and have developed a way to make them work only in hypoxic cells. We obtained funding from the CIHR and Wellcome Trust in the UK to start to develop drugs for use in humans and have succeeded in making several 'lead' compounds that work well, but do not yet have the characteristics of a drug for use in humans.¿LifeArc a UK medical charity is synthesizing new compounds and the proposed research is to select those that are best for use with radiotherapy and ultimately to make a clinical candidate for progression into trials in humans. If successful these new drugs could be transformational and dramatically increase the cure rate of cancers treated by chemotherapy and radiotherapy.