Acute Myeloid Leukemia (AML), a cancer of the myeloid line of blood cells, is the most common type of leukemia in adults (~350.000 new cases yearly worldwide), yet continues to have the lowest overall survival rate of all leukemias (26.9%). Current AML management still relies largely on intensive chemotherapy and stem cell transplantation. Although some AML patients respond to these treatments, most patients that go into remission show disease relapse (up to and 70%). In addition, minimal advances have been made for patients unable to tolerate intensive treatment, for example, older patients. The main objective of our research project was to create a new treatment for acute myeloid leukemia that is (1) more effective and (2) tolerated by all patients. We aimed to use the anticancer natural product beta-lapachone, an under-exploited drug, which we have shown to target the enzyme 5-lipoxygenase in an AML-specific mechanism to treat the cancer. We aimed to develop a new targeting strategy for the drug to guarantee specific uptake of beta-lapachone by AML cells and, importantly, to minimize side effects of the drug on healthy cells. To do this, we aimed to create an antibody-drug conjugate to target the drug to cancer cells. We believe that upon targeting, our drug will not only be more effective than currently used AML therapies, but will also be tolerated by patients unable to tolerate intensive treatments. We propose that inhibition of 5LO by Lap will lead to highly effective specific cancer cell death while sparing healthy cells, thereby yielding maximal efficacy while minimizing toxicity.
