Targeted therapy in acute myeloid leukaemia: current status and future directions

Abstract

Background: The limit of acceptable toxicity for standard chemotherapeutic drugs used in acute myeloid leukaemia (AML) therapy has been reached. New therapeutic strategies are therefore needed. Objective: This review summarizes development in new strategies, and gives an overview of the clinical status on new drugs for non-promyelocytic AML in adults. Methods: Information was principally gathered from the databases ClinicalTrials.gov and PubMed.gov. Results/conclusion: The major improvements in AML treatment during the last two decades has not been the introduction of new therapeutic agents, but rather the more optimal use of well-known drugs (e.g., high-dose cytarabine therapy, the use of ATRA in maintenance therapy of acute promyelocytic leukaemia) and improvement in the diagnosis and treatment of potentially life-threatening complications in patients treated with allogeneic stem cell transplantation. However, further investigations based on specific targeted therapy and stratification of patients according to knowledge of the individual disease and health status will probably be necessary in future studies of new targeted therapy.

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

“…Overall, a CR rate of 67% was achieved and this result is remarkable if we consider that all patients had s-AML; however, CR rate for patients with unfavourable karyotype was only 28% and most of them did ultimately relapse. These data support the need for alternative approaches in older AML patients with adverse karyotype ad presentation independently from clinical eligibility for conventional induction chemotherapy [38][39][40]. Of note, there was no difference in the clinical outcome between patients aged 61-70 years and over 70 years, suggesting that biologic parameters at diagnosis rather than age by itself should be taken into account for the initial therapeutic approach in aged AML patients.…”

Antileukaemic effect of PI3K‐mTOR inhibitors in acute myeloid leukaemia‐gene expression profiles reveal CDC25B expression as determinate of pharmacological effect

“…The overall disease-free survival is only 40-50% even for younger patients below 60-65 years of age who can receive the most intensive chemotherapy, and new therapeutic strategies are thus warranted (Stapnes et al, 2009).…”

“…The improved survival for AML patients during recent decades is not due to the introduction of new therapeutic agents but rather a more optimal use of well-known drugs and improved supportive care for patients receiving intensive antileukaemic therapy (Stapnes et al, 2009). The PI3K-mTOR pathway seems to be important in leukaemogenesis and may therefore be a potential therapeutic target in haematological malignancies (Park et al, 2010;Reikvam et al, 2013a).…”

Normal bone marrow signal-transduction profiles: a requisite for enhanced detection of signaling dysregulations in AML

“…18 In addition, both c-Kit and Flt3 inhibitors are either used clinically or are in various stages of clinical trials. 19 Therefore, these ligand/receptor systems were included as a primary focus. IL-3, G-CSF, and GM-CSF are key regulators of myeloid differentiation, acting primarily through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) regulatory network.…”