Dasatinib as an investigational drug for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

Brattås, Marte Karen; Reikvam, Håkon; Tvedt, Tor Henrik Anderson; Bruserud, Øystein

doi:10.1080/13543784.2019.1597052

Cited by 15 publications

(13 citation statements)

References 81 publications

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“…This explanation is also supported by our previous clinical studies where several patients with high-risk chemoresistant disease according to conventional prognostic criteria (e.g., relapsed AML, previous chronic myeloproliferative neoplasia, complex karyotype) were classified as responders to our ATRA/VP-based treatment regimen [ 4 , 6 ]. A dependency of the prognostic impact of a certain biomarker on the received treatment has also been described in other diseases, e.g., the impact of the BCR-ABL translocation in acute lymphoblastic leukemia (ALL) treated with kinase inhibitors [ 103 ] and especially the Burkit B cell variant of ALL that was originally regarded as a high-risk variant but was later classified as a favorable variant when new therapeutic strategies were introduced [ 104 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Hernandez-Valladares

Wangen

Aasebø

et al. 2021

Cancers

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All-trans retinoic acid (ATRA) and valproic acid (VP) have been tried in the treatment of non-promyelocytic variants of acute myeloid leukemia (AML). Non-randomized studies suggest that the two drugs can stabilize AML and improve normal peripheral blood cell counts. In this context, we used a proteomic/phosphoproteomic strategy to investigate the in vivo effects of ATRA/VP on human AML cells. Before starting the combined treatment, AML responders showed increased levels of several proteins, especially those involved in neutrophil degranulation/differentiation, M phase regulation and the interconversion of nucleotide di- and triphosphates (i.e., DNA synthesis and binding). Several among the differentially regulated phosphorylation sites reflected differences in the regulation of RNA metabolism and apoptotic events at the same time point. These effects were mainly caused by increased cyclin dependent kinase 1 and 2 (CDK1/2), LIM domain kinase 1 and 2 (LIMK1/2), mitogen-activated protein kinase 7 (MAPK7) and protein kinase C delta (PRKCD) activity in responder cells. An extensive effect of in vivo treatment with ATRA/VP was the altered level and phosphorylation of proteins involved in the regulation of transcription/translation/RNA metabolism, especially in non-responders, but the regulation of cell metabolism, immune system and cytoskeletal functions were also affected. Our analysis of serial samples during the first week of treatment suggest that proteomic and phosphoproteomic profiling can be used for the early identification of responders to ATRA/VP-based treatment.

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Section: Discussionmentioning

confidence: 99%

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Hernandez-Valladares

Wangen

Aasebø

et al. 2021

Cancers

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“…With regard to management, the IL-6 receptor blocker tocilizumab, which has been approved by the FDA for the treatment of CRS ( 151 ), is the first-line medication for CRS without affecting the efficacy of CAR T-cells ( 152 ). Other drugs, such as siltuximab (an IL-6 blocker) ( 153 ), anakinra (an IL-1 receptor blocker) ( 154 ), and dasatinib (a tyrosine kinase inhibitor) ( 155 ), have been applied in clinical trials with significant effectiveness. For the administration of corticosteroids, their impact on CAR T-cell activity remains controversial ( 156 , 157 ).…”

Section: Clinical Strategiesmentioning

confidence: 99%

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Huang

Xiao

et al. 2021

Front. Immunol.

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Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.

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“…DASATINIB, nilotinib and bosutinib are second generation BCR-ABL inhibitors [251][252][253][254]. Dasatinib (BMS-354825) was designed by Bristol-Myers Squibb and Otskuka Pharmaceutical Co., Ltd. to inhibit imatinib resistant BCR-ABL mutations in CML but it also works against Src family kinases [255][256][257][258]. The crystal structure of the kinase domain + dasatinib complex shows that the drug makes hydrogen bonds with T315 and M318.…”

Section: Abelson Murine Leukemia Viral Oncogene Homolog 1 (Abl1)mentioning

confidence: 99%

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

Hamid

Petreaca

2020

Cancers

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Secondary resistant mutations in cancer cells arise in response to certain small molecule inhibitors. These mutations inevitably cause recurrence and often progression to a more aggressive form. Resistant mutations may manifest in various forms. For example, some mutations decrease or abrogate the affinity of the drug for the protein. Others restore the function of the enzyme even in the presence of the inhibitor. In some cases, resistance is acquired through activation of a parallel pathway which bypasses the function of the drug targeted pathway. The Catalogue of Somatic Mutations in Cancer (COSMIC) produced a compendium of resistant mutations to small molecule inhibitors reported in the literature. Here, we build on these data and provide a comprehensive review of resistant mutations in cancers. We also discuss mechanistic parallels of resistance.

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Dasatinib as an investigational drug for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

Cited by 15 publications

References 81 publications

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

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