Abstract:
PURPOSE OF REVIEW:Ras pathway mutations are one of the most common type of alterations in pediatric hematologic malignancies and are frequently associated with adverse outcomes. Despite ongoing efforts to use targeted treatments, there remain no Food and Drug Administration (FDA)-approved medications specifically for children with Ras pathway-mutated leukemia. This review will summarize the role of Ras pathway mutations in pediatric leukemia, discuss the current state of Ras pathway inhibitors and highlight the most promising agents currently being evaluated in clinical trials. RECENT FINDINGS:Efficacy using RAF and MEK inhibitors has been demonstrated across multiple solid and brain tumors, and these are now considered standard-of-care for certain tumor types in adults and children. Clinical trials are now testing these medications for the first time in pediatric hematologic disorders, such as acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, and histiocytic disorders. Novel inhibitors of the Ras pathway, including direct RAS inhibitors, are also being tested in clinical trials across a spectrum of pediatric and adult malignancies. SUMMARY:Activation of the Ras pathway is a common finding in pediatric hematologic neoplasms. Implementation of precision medicine with a goal of improving outcomes for these patients will require testing of Ras pathway inhibitors in combination with other drugs in the context of current and future clinical trials.
journal_name
Curr Opin Pediatrjournal_title
Current opinion in pediatricsauthors
Pikman Y,Stieglitz Edoi
10.1097/MOP.0000000000000981subject
Has Abstractpub_date
2021-02-01 00:00:00pages
49-58issue
1eissn
1040-8703issn
1531-698Xpii
00008480-202102000-00008journal_volume
33pub_type
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journal_title:Current opinion in pediatrics
pub_type: 杂志文章,评审
doi:10.1097/MOP.0b013e328320acea
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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journal_title:Current opinion in pediatrics
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