Phase 1 study of the angiopoietin 1/2 neutralizing peptibody, trebananib, in acute myeloid leukemia.

Wang, Eunice S.; Fetterly, Gerald J.; Pitzonka, Laura; Brady, William E.; Tan, Wei; Greene, Jessica Davila; Munster, Deborah; Vigil, Carlos Enrique; Mendler, Jason H.; Becker, Michael W.; Carr-O'Dwyer, Kristen Marie; Wetzler, Meir; Liesveld, Jane L.

doi:10.1200/jco.2014.32.15_suppl.7082

Cited by 5 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, high expression of the pro-angiogenic factor Ang2 is an independent prognostic factor for overall survival in AML ( 122 ). However, clinical studies with trebananib, a neutralizing peptibody against Ang1 and Ang2 showed only a limited clinical efficacy ( 123 ). Overall, clinical data indicates that monotherapy with antiangiogenic drugs lack the efficacy to treat aggressive leukemia's, only the combination of antiangiogenic drugs with standard chemotherapy is likely to have a benefit for patient's outcome and need more clinical investigations.…”

Section: Antiangiogenic Therapy Of Amlmentioning

confidence: 99%

Acute Myeloid Leukemia and the Bone Marrow Niche—Take a Closer Look

2018

View full text Add to dashboard Cite

The bone marrow is the home of hematopoiesis and is therefore a hotspot for the development of hematopoietic diseases. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells must find a balance between proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation, leading to hematopoietic diseases. Here we focus on acute myeloid leukemia (AML), since this is the most frequent acute leukemia in adulthood with very poor overall survival rates and where relapse after chemotherapy continues to be a major challenge, driving demand for new therapeutic strategies. Current research is focusing on the identification of specific interactions between leukemic blasts and their niche components, which may be exploited as novel treatment targets along with induction chemotherapy. Significant progress has been gained over the last few years in the field of high-resolution imaging. Confocal ex vivo and intravital microscopy have revealed a detailed map of bone marrow structures and components; as well as identifying numerous alterations in the stem cell niche that correspond to disease progression. However, the underlying mechanisms are still not completely understood and due to the complexity, their elucidation remains a challenging. This review discusses the constitution of the AML niche in the bone marrow, the improvement in visualization of the complex three-dimensional niche structures and points out new therapeutic strategies to increase the overall survival of AML patients.

show abstract

Section: Antiangiogenic Therapy Of Amlmentioning

confidence: 99%

Acute Myeloid Leukemia and the Bone Marrow Niche—Take a Closer Look

2018

View full text Add to dashboard Cite

show abstract

“…It has been trialed in a range of mostly solid cancers, but has shown promise in preclinical AML models. A phase 1b trial of trebananib with or without cytarabine reported tolerable safety profile and lack of neutralizing antibody formation, but only a single PR among 24 AML patients ( Wang E.S. et al, 2014 ).…”

Section: Therapeutic Targeting Of the Vascular Nichementioning

confidence: 99%

The Dynamic Interface Between the Bone Marrow Vascular Niche and Hematopoietic Stem Cells in Myeloid Malignancy

Mosteo

Storer

Batta

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Hematopoietic stem cells interact with bone marrow niches, including highly specialized blood vessels. Recent studies have revealed the phenotypic and functional heterogeneity of bone marrow endothelial cells. This has facilitated the analysis of the vascular microenvironment in steady state and malignant hematopoiesis. In this review, we provide an overview of the bone marrow microenvironment, focusing on refined analyses of the marrow vascular compartment performed in mouse studies. We also discuss the emerging role of the vascular niche in “inflamm-aging” and clonal hematopoiesis, and how the endothelial microenvironment influences, supports and interacts with hematopoietic cells in acute myeloid leukemia and myelodysplastic syndromes, as exemplar states of malignant myelopoiesis. Finally, we provide an overview of strategies for modulating these bidirectional interactions to therapeutic effect in myeloid malignancies.

show abstract