Progress of FLT3 Protein Degradation-Targeting Chimeras for the Treatment of Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is a highly heterogeneous and aggressive haematological malignancy that is often difficult to treat due to mutations in the FLT3 gene. Several small molecule inhibitors have been developed, but they can easily cause patients to develop new point mutations, which can result in drug resistance leading to relapse, high adverse effects and poor prognosis in AML. Therapeutic strategies against FLT3 are constantly being innovated, and PROTAC (protein cleavage-targeted chimerism), a novel therapeutic modality, has demonstrated superiority over traditional small-molecule inhibitors by inducing the degradation of target proteins, especially in terms of target selectivity and drug degradation efficiency. Studies have shown that FLT3-PROTAC can efficiently degrade FLT3 proteins and reduce the emergence of drug resistance, making it a new hope for the treatment of FLT3-mutant AML.