Molecular therapy for acute myeloid leukaemia

Coombs, Catherine C.; Tallman, Martin S.; Levine, Ross L.

doi:10.1038/nrclinonc.2015.210

Cited by 113 publications

(83 citation statements)

References 150 publications

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“…Sadly, treatment for AML patients has not changed much since the 1970s, despite the wealth of knowledge accumulated since then 11, 12 . Standard chemotherapy for patients, the “7+3” combination of cytarabine and daunorubicin infusion, can induce complete remission in approximately 80% of patients under 60 years of age 13 .…”

Section: Background and Introductionmentioning

confidence: 99%

The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia

Tan

Pearson

Feith

2017

Expert Opinion on Therapeutic Targets

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Introduction Acute myeloid leukemia (AML) is the most common adult leukemia. Only a fraction of AML patients will survive with existing chemotherapy regimens. Hence, there is an urgent and unmet need to identify novel targets and develop better therapeutics in AML. In the past decade, the field of sphingolipid metabolism has emerged into the forefront of cancer biology due to its importance in cancer cell proliferation and survival. In particular, acid ceramidase (AC) has emerged as a promising therapeutic target due to its role in neutralizing the pro-death effects of ceramide. Areas covered This review highlights key information about AML biology as well as current knowledge on dysregulated sphingolipid metabolism in cancer and AML. We describe AC function and dysregulation in cancer, followed by a review of studies that report elevated AC in AML and compounds known to inhibit the enzyme. Expert opinion AML has a great need for new drug targets and better therapeutic agents. The finding of elevated AC in AML supports the concept that this enzyme represents a novel and realistic therapeutic target for this common leukemia. More effort is needed towards developing better AC inhibitors for clinical use and combination treatment with existing AML therapies.

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Section: Background and Introductionmentioning

confidence: 99%

The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia

Tan

Pearson

Feith

2017

Expert Opinion on Therapeutic Targets

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“…This makes it a priority to establish rapid molecular diagnostics in the clinical setting so that results can influence treatment decisions in real time. 19 There is much speculation on the possibilities of personalised therapy; while current therapeutic strategies are based on genetic analysis to some degree, treatment categories remain rather broad because there are few first-line treatment options and knowledge of how particular genetic mutations affect treatment response is incomplete. Navigating the vast array of novel drugs will be a considerable challenge for haematologists in the years to come.…”

Section: Discussionmentioning

confidence: 99%

“…17,19 It is therefore likely that to achieve lasting responses kinase inhibitors will need to be used in combination with other therapies.…”

Section: S49mentioning

confidence: 99%

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From genomics to targeted treatment in haematological malignancies: a focus on acute myeloid leukaemia

Jakobsen

Vyas

2018

Clinical Medicine

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The haematological malignancies are a heterogeneous group of neoplastic disorders, which lead to almost 10,000 deaths annually in the UK. Over the past 2 decades, there has been significant progress in our understanding of the pathological mechanisms underlying these cancers, accompanied by improvements in outcomes for some patients. In particular, advances in next-generation sequencing now make it possible to define the genetic lesions present in each patient, which has led to improved disease classification, risk stratification and identification of new therapeutic targets. Here we discuss recent advances in the genomic classification and targeted treatment of haematological malignancies, focusing on acute myeloid leukaemia. Multiple novel drug classes are now on the horizon, including agents that target overactive signalling pathways, differentiation therapies and immunotherapies. By combining molecular diagnostics with targeted therapy, the management of these diseases is set to change radically over the coming years.

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“…[150][151][152][153][154][155] In addition, achieving deep CR without MRD is of key importance for assessment of clinical outcomes. [155][156][157] MFC-and PCR-based technologies allow a highly sensitive (0.1%-0.001%), objective, and standardized assessment of treatment response over time (Figure 2A; Table 3).…”

Section: Noninvasive Disease Detection In Myeloid Malignanciesmentioning

confidence: 99%

High-throughput sequencing for noninvasive disease detection in hematologic malignancies

Scherer

Kurtz

Diehn

et al. 2017

Blood

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Noninvasive monitoring of minimal residual disease (MRD) has led to significant advances in personalized management of patients with hematologic malignancies. Improved therapeutic options and prolonged survival have further increased the need for sensitive tumor assessment that can inform treatment decisions and patient outcomes. At diagnosis or relapse of most hematologic neoplasms, malignant cells are often easily accessible in the blood as circulating tumor cells (CTCs), making them ideal targets to noninvasively profile the molecular features of each patient. In other cancer types, CTCs are generally rare and noninvasive molecular detection relies on circulating tumor DNA (ctDNA) shed from tumor deposits into circulation. The ability to precisely detect and quantify CTCs and ctDNA could minimize invasive procedures and improve prediction of clinical outcomes. Technical advances in MRD detection methods in recent years have led to reduced costs and increased sensitivity, specificity, and applicability. Among currently available tests, high-throughput sequencing (HTS)–based approaches are increasingly attractive for noninvasive molecular testing. HTS-based methods can simultaneously identify multiple genetic markers with high sensitivity and specificity without individual optimization. In this review, we present an overview of techniques used for noninvasive molecular disease detection in selected myeloid and lymphoid neoplasms, with a focus on the current and future role of HTS-based assays.

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Molecular therapy for acute myeloid leukaemia

Cited by 113 publications

References 150 publications

The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia

The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia

From genomics to targeted treatment in haematological malignancies: a focus on acute myeloid leukaemia

High-throughput sequencing for noninvasive disease detection in hematologic malignancies

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