The blind men and the AML elephant: can we feel the progress?

Abstract

The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline–cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems.

Epigenome-Based Drug Repositioning in Acute Myeloid Leukemia

“…We posited that the most clear demonstration of utility for our method would be to correctly predict significance for the most commonly used AML therapy, cytarabine, which has remained the frontline therapy for over 30 years, and which is broadly effective against all subtypes of AML [31,32] . Indeed, our method did correctly identify cytarabine as highly significant in both datasets examined; however, our method did not identify either daunorubicin or idarubicin, two anthracycline chemotherapeutics that are commonly co-prescribed with cytarabine [31,33] .…”

Combining empirical knowledge, in silico molecular docking and ADMET profiling to identify therapeutic phytochemicals from Brucea antidysentrica for acute myeloid leukemia

“…The result in older patients who are unable to receive intensive chemotherapy is very bad with a median survival of only 5 to 10 months [ 7 ]. Although there has been some increase in survival for younger patients through better management of therapy-related toxicities, stem cell transplantation and emergence of some targeted drugs, AML’s therapy has largely remained unchanged for over four decades [ 8 ] and is still an active topic of research. Recent advances in high-throughput technologies enabled the elucidation of genetics and pathophysiology leading to detection of recurrent molecular mutations [ 9 ] in AML.…”

Novel CD123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics

“…These features may generate serious problematic side effects such as limited drug intensity, duration of chemotherapy and reduced therapeutic efficacy (Cornelissen & Blaise, 2016 ; Yeung & Radich, 2017 ). These disadvantages may result in treatment failure, relapse and poor prognosis (Shlush & Mitchell, 2015 ; Benito et al., 2016 ; Tauro, 2016 ). To circumvent these problems, there is an urgent need to develop novel AML therapeutic strategies with higher efficacy and accuracy.…”