Research Theme within School of Biosciences:Molecular and Cell Biology
Translational leukaemia and lymphoma research
Exploitation of differentiation and apoptosis patways in the development of therapies for haematological malignancies
Improved chemotherapy and marrow transplantations have radically improved survival and cure rates in children and young adults suffering from leukaemia and lymphoma. However, as we get older our bodies become less able to withstand these therapies resulting in much poorer cure rates in older patients. For example median survival in acute myeloid leukaemia (AML), which is a disease predominantly of adults, remains less than six months.
Chemotherapy induces apoptosis of tumour cells via causing them physical damage. However, this damage is not restricted to the tumour cells resulting in systemic toxicity. We are trying to develop novel therapies that trigger apoptosis and/or differentiation in tumour cells using drugs that interact directly with these pathways and which do not directly damage cells. We are exploring avenues for exploiting the powerful anti-tumour activities of the cyclopentenone prostaglandin 15deoxy Delta 12,14PGFJ2 in leukaemia cells. A central theme in the work is the exploitation of an enzyme of the aldo-ketoreductase family (AKR1C3). This enzyme indirectly prevents 15deoxy Delta 12,14PGFJ2 synthesis. Our laboratory based studies have demonstrated that Inhibitors of this enzyme show anti-tumour activity against leukaemia and lymphoma cells. We are therefore investigating their activity in clinical trials.
A particular focus is the use of old drugs for new diseases. New drug discovery progresses at a dismally slow pace and is phenomenally expensive, placing costly burdens on systems of health provision when they do arise and neglecting all but the richest nations. Drug redeployment endeavours to use relatively cheap available drugs and to use them in new ways. Our approach is to take drugs that are not considered as anti-cancer drugs and to use them in combinations that generate an anti-cancer effect. Our most advanced project is the use of the contraceptive drug medroxyprogesterone acetate combined with a cholesterol lowering drug Bezafibrate. This remarkable drug combination is now in clinical Trials for the treatment of AML here in the UK and in Burkitt lymphoma in Malawi.