Targeted and epigenetic therapies for acute myeloid leukemia treatment.

This article provides a comprehensive overview of targeted and epigenetic therapies for acute myeloid leukemia (AML), highlighting their role in advancing treatment strategies. Recognizing that AML arises from complex genetic and epigenetic alterations, a deeper understanding of its pathogenesis has paved the way for precision medicine. The article reviews key targeted therapies, including IDH inhibitors (e.g., ivosidenib, enasidenib) for IDH mutations, FLT3 inhibitors (e.g., midostaurin, gilteritinib) for FLT3 alterations, BCL2 inhibitors (e.g., venetoclax) impacting apoptosis, and emerging Menin inhibitors for specific subtypes like KMT2A-rearranged or NPM1-mutant AML. It also discusses epigenetic therapies that target reversible changes, such as DNMT inhibitors (e.g., azacitidine, decitabine) for DNA methylation and HDAC inhibitors for histone modifications, along with other promising agents under development targeting epigenetic regulators. Furthermore, the article explores gene therapy as a significant future direction, detailing advancements in gene editing (CRISPR/Cas9) and strategies designed to shield healthy hematopoietic cells from targeted toxicity (e.g., CD33, CD123 editing) or to enhance the anti-leukemic function of immune cells (e.g., CAR-T, TCR therapy). The future perspective emphasizes the importance of developing synergistic combination therapies and leveraging molecular insights for truly personalized treatment approaches to overcome therapeutic challenges and improve long-term outcomes for AML patients.