Acute myeloid leukemia – strategies and challenges for targeting oncogenic Hedgehog/GLI signaling

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• 作者：Fritz Aberger ; Evelyn Hutterer ; Christina Sternberg…
• 关键词：Acute myeloid leukemia ; Cancer stem cells ; Hedgehog (HH) signaling ; GLI proteins ; Non ; canonical Hedgehog/GLI signaling ; Combination therapy
• 刊名：Cell Communication and Signaling
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：15
• 期：1
• 全文大小：1036KB
• 刊物主题：Cell Biology; Protein-Ligand Interactions; Receptors; Cytokines and Growth Factors;
• 出版者：BioMed Central
• ISSN：1478-811X
• 卷排序：15

文摘

Treatment of acute myeloid leukemia (AML), an aggressive and heterogeneous hematological malignancy, remains a challenge. Despite advances in our understanding of the complex genetics and biology of AML pathophysiology, these findings have been translated to the clinic with only limited success, and poor outcomes persist for the majority of patients. Thus, novel treatment strategies are clearly needed for achieving deeper and prolonged remissions and for avoiding the development of resistance. Due to its profound role in (cancer) stem cell biology and differentiation, the Hedgehog (HH)/Glioma-associated Oncogene Homolog (GLI) signaling pathway may be an attractive novel therapeutic target in AML. In this review, we aim to provide a critical and concise overview of the currently known potential and challenges of HH/GLI targeting. We describe the biological role of the HH/GLI pathway in AML pathophysiology. We specifically focus on ways of targeting non-canonical HH/GLI signaling in AML, particularly in combination with standard treatment regimens, which may overcome some hurdles observed with approved HH pathway inhibitors in solid tumors.