Home2020Researchers from CSI Singapore & ASLAN Pharmaceuticals Make Headway in the Treatment of Acute Myeloid Leukemia.
Researchers from CSI Singapore & ASLAN Pharmaceuticals Make Headway in the Treatment of Acute Myeloid Leukemia.
Acute Myeloid Leukemia (AML) is a common and aggressive blood cancer and has a relatively poor overall survival rate. Characterized by an overproduction of immature white blood cells, AML has limited treatment options, with chemotherapy being the main therapeutic approach that is currently available. However, chemotherapy is non-selective, which kills fast-dividing leukemic cells as well as normal cells throughout the body, leading to severe and sometimes intolerable side effects experienced by patients. More importantly, prolonged usage could also set the stage for drug resistance and relapse.
In this pioneering study performed by researchers from CSI Singapore and ASLAN Pharmaceuticals, the team has made a quantum leap in the development of effective therapeutic modalities for AML. ASLAN003, a new anti-leukemia drug, is said to have less toxicity to normal bone marrow cells compared to chemotherapy. The drug’s potential for treating AML was discovered by research team headed by Professor Chng Wee Joo from CSI Singapore and the National University Health System (NUHS).
“For a long time, the identification of effective differentiation therapies for acute leukemias other than acute promyelocytic leukemia has been challenging. In addition, ASLAN003 appears to have an effective differentiation therapy for other subtypes of leukemia in our pre-clinical studies. These exciting results are now being translated into the clinics with a clinical trial that involves patients from Singapore and Australia,” said Professor Chng.
ASLAN003 is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), a key enzyme for pyrimidine biosynthesis. Results demonstrate that ASLAN003 could induce differentiation in arrested leukemia cells, allowing the resumption of normal maturation processes.
Dr Zhou Jianbiao, the first author of the paper, explained, “Our research focuses on a therapy that reverses the differentiation block of these immature cells and let them mature. This kind of differentiation therapy will have the same effectiveness as chemotherapy, but with much less side-effects.”
Moving forward, ASLAN003 is currently being evaluated in Singapore (National University Hospital and Singapore General Hospital), as well as 8 centres in Australia. Dr Mark McHale, Head of R&D from ASLAN Pharmaceuticals, added, “We have recruited 24 patients in the clinical trial with good responses and a stable disease was achieved with ASLAN003 monotherapy. The next step is to combine ASLAN003 with other drugs to treat AML patients.”