Towards precision medicine for AML.
Hartmut DöhnerAndrew H WeiBob LöwenbergPublished in: Nature reviews. Clinical oncology (2021)
With rapid advances in sequencing technologies, tremendous progress has been made in understanding the molecular pathogenesis of acute myeloid leukaemia (AML), thus revealing enormous genetic and clonal heterogeneity, and paving the way for precision medicine approaches. The successful development of precision medicine for patients with AML has been exemplified by the introduction of targeted FLT3, IDH1/IDH2 and BCL-2 inhibitors. When used as single agents, these inhibitors display moderate antileukaemic activity. However, augmented clinical activity has been demonstrated when they are administered in combination with drugs with broader mechanisms of action targeting epigenetic and/or other oncogenic signalling pathways or with conventional cytotoxic agents. The development of immunotherapies has been hampered by the expression of antigens that are expressed by both leukaemic and non-malignant haematopoietic progenitor cells; nonetheless, a diverse range of immunotherapies are now entering clinical development. This myriad of emerging agents also creates challenges, such as how to safely combine agents with different mechanisms of action, the need to circumvent primary and secondary resistance, and new challenges in future clinical trial design. In this Review, we discuss the current state of precision medicine for AML, including both the potential to improve patient outcomes and the related challenges.
Keyphrases
- acute myeloid leukemia
- clinical trial
- allogeneic hematopoietic stem cell transplantation
- single cell
- poor prognosis
- dendritic cells
- gene expression
- low grade
- cancer therapy
- drug induced
- liver failure
- high intensity
- genome wide
- long non coding rna
- quantum dots
- study protocol
- high grade
- aortic dissection
- acute respiratory distress syndrome
- human health