AKR1C3 overexpression has been reported in various types of cancers, including T-ALL. AST-006 (TH-3424), an AKR1C3-specific prodrug, was reported recently to have potent cytotoxicity against liver cancer cells overexpressing AKR1C3 and T-ALL. In this study, AST-006 demonstrated potent anti-tumor activity against different T-ALL cell lines in vitro and in vivo, including patient-derived xenograft (PDX) model. AST-006 also exhibited minimal cytotoxicity against primary human T-cells in vitro and lymphocytes in cynomolgus monkeys in vivo, indicating that AST-006 is a promising therapeutic for T-ALL.
Keywords: AKR1C3; AST-006; B-ALL; T-ALL; biomarker; prodrug.