Translating recent advances in the pathogenesis of acute myeloid leukemia to the clinic.
Ontology highlight
ABSTRACT:
SUBMITTER: Bewersdorf JP
PROVIDER: S-EPMC8973851 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor outcome; overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. Recently, significant improvements have been made in our understanding of AML biology and genetics. These fundamental discoveries are now being translated into new therapies for this disease. This review will discuss recent advances in AML biology and the emerging treatments that are arising from biological studies. Specifically, we will consider new therapies that target molecular mutations in AML and dysregulated pathways such as apoptosis and mitochondrial metabolism. We will also discuss recent advances in immune and cellular therapy for AML.
| S-EPMC5621868 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities. In this regard, the classification of AML subtypes has recently evolved from a morphologic to a molecular and genetic basis, reflected by recent updates from the World Health Organization and the new International Consensus Classification system. After years of stagnation in new drug approvals for AML, there has been a rapid expansion of the armamentarium against this disease since 2017. Low-intensity induction therapy with hypomethylating agents and venetoclax has substantially improved outcomes, including in those previously considered to have a poor prognosis. Furthermore, targeted oral therapies against driver mutations in AML have been added to the repertoire. But with an accelerated increase in treatment options, several questions arise such as how to best sequence therapy, how to combine therapies, and if there is a role for maintenance therapy in those who achieve remission and cannot undergo alloHSCT. Moreover, certain subtypes of AML, such as those with TP53 mutations, still have dismal outcomes despite these recent advances, underscoring an ongoing unmet need and opportunity for translational advances. In this review, we will discuss recent updates in the classification and risk stratification of AML, explore the literature regarding low-intensity and novel oral combination therapies, and briefly highlight investigative agents currently in early clinical development for high-risk disease subtypes.
| S-EPMC10039574 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a devastating hematologic malignancy that affects both older adults as well as children. Treatments available for AML largely depend on cytotoxic agents and often the only curative option is an allogeneic bone marrow transplant, an option limited to young persons and associated with high morbidity and mortality. There is an urgent need for the identification of new myeloid targets and an understanding of the key genetic mutations involved in disease progression and prognosis. One such mutation is the internal tandem duplication (ITD) in the FMS-like tyrosine kinase receptor-3 (FLT3) gene which confers an inferior outcome that is attributed to a higher relapse rate. In this review, we evaluate the FLT3-ITD mutation and discuss the recent data regarding emerging approaches using FLT3 inhibitors for the treatment of AML.
| S-EPMC4923501 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease that has a poor prognosis. Recent advances in genomics and molecular biology have led to a greatly improved understanding of the disease. Until 2017, there had been no new drugs approved for AML in decades. Here, we review novel drug targets in AML with a focus on epigenetic-targeted therapies in pre-clinical and clinical development as well as the recent new drug approvals.
| S-EPMC6081972 | biostudies-literature
Project description:Selective inhibitors of nuclear export (SINE) are emerging as a potentially efficacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. SINE specifically block the protein Exportin 1, also known as chromosomal region maintenance 1, leading to nuclear retention of cargo proteins, including several tumor suppressor proteins. Selinexor, a first generation SINE, is currently in early phase clinical studies in various combinations with promising antileukemic and pro-apoptotic activity. Here we discuss the mechanism of action of SINEs and further elaborate on the clinical data available from the various trials in acute myeloid leukemia.
| S-EPMC6219429 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy, characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. The new drugs used for treating AML are facing a big challenge, and the candidates include cytotoxic drugs, targeted small-molecule inhibitors, and monoclonal antibodies. In recent years, active research has focused on several new agents for including them in the large antileukemic drug family. This review aims to introduce some of these new drugs and highlights new advances made in the old drugs, mainly in the last 5 years.
| S-EPMC5933364 | biostudies-other
Project description:Although complete remission rate of B cell acute lymphoblastic leukemia (B-ALL) has improved significantly over the past few decades, patients with relapsed/refractory ALL still have dismal outcome. Tyrosine kinase inhibitors, antibody-drug conjugates and chimeric antigen receptor T cell therapy are changing the therapy landscape for B- ALL. Blinatumomab, a bi-specific T cell engager, has been approved for patients with relapsed/refractory and minimal residual disease positive B-ALL. This review summarized data from recent clinical trials of blinatumomab for B-ALL treatment.
| S-EPMC6833142 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with an incidence that increases with age, and a generally poor prognosis. The disease is clinically and genetically heterogeneous, and recent advances have improved our understanding of the cytogenetic abnormalities and molecular mutations, aiding in prognostication and risk stratification. Until recently, however, therapeutic options were mostly limited to cytotoxic chemotherapy. Since 2017, there has been an explosion of newly approved treatment options both nationally and internationally, with the majority of new drugs targeting specific gene mutations and/or pivotal cell survival pathways. In this review article, we will discuss these new agents approved for the treatment of AML within the last 2 years, and will outline the mechanistic features and clinical trials that led to their approvals.
| S-EPMC6749668 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a clonal malignancy characterized by genetic heterogeneity due to recurrent gene mutations. Treatment with cytotoxic chemotherapy has been the standard of care for more than half of a century. Although much progress has been made toward improving treatment related mortality rate in the past few decades, long term overall survival has stagnated. Exciting developments of gene mutation-targeted therapeutic agents are now changing the landscape in AML treatment. New agents offer more clinical options for patients and also confer a more promising outcome. Since Midostaurin, a FLT3 inhibitor, was first approved by US FDA in 2017 as the first gene mutation-targeted therapeutic agent, an array of new gene mutation-targeted agents are now available for AML treatment. In this review, we will summarize the recent advances in gene mutation-targeted therapies for patients with AML.
| S-EPMC7238648 | biostudies-literature
Project description:The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML) is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years.Within this manuscript, we review the recent developments and the current status of the five currently most prominent immunotherapeutic concepts: (1) antibody-drug conjugates, (2) T cell-recruiting antibody constructs, (3) chimeric antigen receptor (CAR) T cells, (4) checkpoint inhibitors, and (5) dendritic cell vaccination. We focus on the clinical data that has been published so far, both for newly diagnosed and refractory/relapsed AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic stem cell transplantation. Besides, we have included important clinical trials that are currently running or have recently been completed but are still lacking full publication of their results.While each of the concepts has its particular merits and inherent problems, the field of immunotherapy of AML seems to have taken some significant steps forward. Results of currently running trials will reveal the direction of further development including approaches combining two or more of these concepts.
| S-EPMC5526264 | biostudies-literature