Targeting of cell metabolism in human acute myeloid leukemia--more than targeting of isocitrate dehydrogenase mutations and PI3K/AKT/mTOR signaling?

Abstract:

:Targeting of cellular metabolism has emerged as a possible strategy in the treatment of human malignancies, and several experimental studies suggest that this therapeutic approach should also be considered in acute myeloid leukemia (AML). Clinical studies of metabolic intervention in AML patients with isocitrate dehydrogenase mutations have shown promising results. Moreover, metabolic targeting of the PI3K/AKT/mTOR signaling pathway as an anticancer strategy has been extensively studied. In this review, we focus on other emerging therapeutic alternatives for metabolic inhibition in human AML, in particular targeting of glycolysis and the AMP kinase signaling pathway. Pharmacological drugs for these metabolic interventions are already available and they seem to have an acceptable toxicity, even when used in combination with conventional chemotherapy. Future clinical studies of these therapeutic strategies should focus on the following: (i) heterogeneity of patients and the possibility that this treatment is most effective only for certain subsets of patients, (ii) toxic effects in AML patients with an existing disease-induced bone marrow failure prior to treatment, and (iii) whether this strategy should be used as part of a potentially curative treatment and/or as disease-stabilizing treatment to prolong survival in elderly or unfit patients.

journal_name

Eur J Haematol

authors

Hauge M,Bruserud Ø,Hatfield KJ

doi

10.1111/ejh.12690

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

211-21

issue

3

eissn

0902-4441

issn

1600-0609

journal_volume

96

pub_type

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