Co-applicant: Dr. Michael Rauh
Small molecule targeting of CYP26B1 in myeloid leukaemia
Retinoic Acid (RA) has been used since the 1980s to treat certain types of blood cancers. AML is a blood cancer characterized by the growth and accumulation of immature cells, known as blasts, in the bone marrow and blood. RA is able to change the blast cells that cause cancer in a way which limits their cancer-causing potential but, unfortunately, it has been unsuccessful for treating Acute Myeloid Leukemia (AML). The cells for this type of cancer are protected by bone marrow cells which rapidly metabolize RA due to activity of a protein called CYP26, discovered previously in our lab. We believe that compounds that block the CYP26 in these patients will restore the therapeutic effects of RA. We have designed and developed a series of potential drugs which are able to block CYP26. We have found that that blocking CYP26 can be an effective strategy to sensitize leukemic cells to RA. This would be the first drug of its kind for treating MDS (a precursor of AML) and AML, and could completely revolutionize treatment for these patients and significantly increase the rate of remission.