Importance of targeted therapies in acute myeloid leukemia

Conventional chemotherapy nonspecifically targets leukemic cells, which increases the risk of other health problems. However, increased understanding of molecular pathways in leukemic cells, as well as the role of bone marrow niche in leukemia, has come with the opportunity to develop targeted therapies that promise to be both more effective and less toxic than current chemotherapy. Specific target identification (target discovery) requires different strategies and technologies. These strategies can be broadly divided into two groups: “molecular” and “systems” approach. Molecular approach uses in vitro models, proteomics, genomics, and genetic association for target discovery while systems approach uses clinical and in vivo models to identify potential targets. Recently, targets such as histone deacetylase, FLT3, IDH1/2 are under investigation for developing drugs toward specific leukemia subtypes. However, biological research has not been that successful in discovering novel targets for leukemia as it was expected. In addition to many technical difficulties, probably the most significant problem in relation to target discovery in leukemia is the involvement of multiple pathways and the presence of leukemic stem cells that are presently the main focus of many biotechnology research. This chapter discusses the strategies and methodologies being used for the identification of novel targets and pathways in leukemia. These include recent technological advances in the fields of genomics and proteomics, as well as targeted delivery systems. Currently approved therapies and those in clinical trials are discussed along with prevailing challenges in acute myeloid leukemia treatment.