Understanding mechanisms of resistance to FLT3 inhibitors in adult FLT3-mutated acute myeloid leukemia to guide treatment strategy

Ruglioni, Martina; Crucitta, Stefania; Luculli, Giovanna Irene; Tancredi, Gaspare; Del Giudice, Maria Livia; Mechelli, Sandra; Galimberti, Sara; Danesi, Romano; Del Re, Marzia

doi:10.1016/j.critrevonc.2024.104424

Critical Reviews in Oncology/Hematology

2024

DOI: 10.1016/j.critrevonc.2024.104424

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Understanding mechanisms of resistance to FLT3 inhibitors in adult FLT3-mutated acute myeloid leukemia to guide treatment strategy

Martina Ruglioni,

Stefania Crucitta,

Giovanna Irene Luculli

et al.

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Cited by 4 publications

References 198 publications

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Advances in the pathogenesis of FLT3-mutated acute myeloid leukemia and targeted treatments

Travaglini,

Gurnari,

Ottone

et al. 2024

Current Opinion in Oncology

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Purpose of review FLT3 mutations are among the most common myeloid drivers identified in adult acute myeloid leukemia (AML). Their identification is crucial for the precise risk assessment because of the strong prognostic significance of the most recurrent type of FLT3 alterations, namely internal tandem duplications (ITDs). Recent advances in the pathogenesis and biology of FLT3-mutated AML have opened an opportunity for development and application of selective inhibition of FLT3 pathway. Recent findings In the last decade, at least three targeted treatments have been approved by regulatory agencies and several others are currently under investigations. Here, we review the latest advance in the role of FLT3 mutations in AML, providing an outline of the available therapeutic strategies, their mechanisms of actions and of resistance, as well as routes for potential improvement. Summary The availability of FLT3 inhibitors has improved outcomes in AML harboring such mutations, currently also reflected in disease stratification and recommendations. Newer inhibitors are under investigations, and combinations with chemotherapy or other targeted treatments are being explored to further improve disease outcomes.

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Advances in the pathogenesis of FLT3-mutated acute myeloid leukemia and targeted treatments

Travaglini,

Gurnari,

Ottone

et al. 2024

Current Opinion in Oncology

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Gene regulatory network and signalling pathway rewiring: How blood cancer cells shift their shapes to evade drug treatment

Bonifer,

Cockerill

2024

Oncotarget

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Molecular Features and Treatment Paradigms of Acute Myeloid Leukemia

Shukla,

Abdul-Hay,

Choi

2024

Biomedicines

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Acute myeloid leukemia (AML) is a common hematologic malignancy that is considered to be a disease of aging, and traditionally has been treated with induction chemotherapy, followed by consolidation chemotherapy and/or allogenic hematopoietic stem cell transplantation. More recently, with the use of next-generation sequencing and access to molecular information, targeted molecular approaches to the treatment of AML have been adopted. Molecular targeting is gaining prominence, as AML mostly afflicts the elderly population, who often cannot tolerate traditional chemotherapy. Understanding molecular changes at the gene level is also important for accurate disease classification, risk stratification, and prognosis, allowing for more personalized medicine. Some mutations are well studied and have an established gene-specific therapy, including FLT3 and IDH1/2, while others are being investigated in clinical trials. However, data on most known mutations in AML are still minimal and therapeutic studies are in pre-clinical stages, highlighting the importance of further research and elucidation of the pathophysiology involving these genes. In this review, we aim to highlight the key molecular alterations and chromosomal changes that characterize AML, with a focus on pathophysiology, presently available treatment approaches, and future therapeutic options.

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Understanding mechanisms of resistance to FLT3 inhibitors in adult FLT3-mutated acute myeloid leukemia to guide treatment strategy

Cited by 4 publications

References 198 publications

Advances in the pathogenesis of FLT3-mutated acute myeloid leukemia and targeted treatments

Advances in the pathogenesis of FLT3-mutated acute myeloid leukemia and targeted treatments

Gene regulatory network and signalling pathway rewiring: How blood cancer cells shift their shapes to evade drug treatment

Molecular Features and Treatment Paradigms of Acute Myeloid Leukemia

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