Protein kinase inhibitors for acute leukemia

Yuan, Ling; Xie, Qing; Zhang, Zikang; Zhang, Hua

doi:10.1186/s40364-018-0123-1

Cited by 29 publications

(26 citation statements)

References 78 publications

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“…It will be important to determine whether the combination approach will be functional in other BCR-Abl-positive leukemias, such as acute lymphoblastic leukemia that sometimes presents a BCR-Abl-positive phenotype. It remains to be seen whether other protein kinase inhibitors and antibodies can be explored as a synergistic pair with BCR-Abl siRNAs to develop a replacement for conventional therapies against drug-resistant CML phenotypes [49,50].…”

Section: Combination Therapy For CML 741mentioning

confidence: 99%

BCR-AblSilencing by siRNA: A Potent Approach to Sensitize Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitor Therapy

Thapa

Ubeda

et al. 2019

Stem Cells and Development

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Nonviral gene therapy with specific short interfering RNAs (siRNAs) against BCR-Abl can be an alternative and/or supportive therapy of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs), given the often observed resistance to TKIs in clinical setting. In this study, we explored the feasibility of BCR-Abl siRNA therapy in CML K562 cells in vitro by employing a cationic polymer derived from cholesterol (Chol) grafted low-molecular weight polyethyleneimine (PEI). The first generation TKI imatinib upregulated the expression of BCR-Abl in K562 cells as expected. Delivery of BCR-Abl siRNA in both drug-sensitive and drugresistant K562 cells significantly downregulated the mRNA levels in both cell types. Similarly, the BCR-Abl siRNA treatment arrested the growth of both drug-sensitive and drug-resistant K562 cells with no obvious differences despite a large difference in drug responsiveness. The BCR-Abl gene silencing in combination with TKI treatments exhibited significant synergism in drug-resistant K562 cells in generating substantial antileukemic activity, where the TKIs on their own were not effective. The effect of BCR-Abl siRNA and TKIs on non-CML cells ( Jurkat and primary fibroblast) was negligible, indicating the specificity of the proposed therapy. This strategy can significantly overcome TKI resistance in CML cells, suggesting a feasible and effective treatment model for CML patients suffering from clinical resistances.

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Section: Combination Therapy For CML 741mentioning

confidence: 99%

BCR-AblSilencing by siRNA: A Potent Approach to Sensitize Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitor Therapy

Thapa

Ubeda

et al. 2019

Stem Cells and Development

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“…17 Second-generation FLT3 inhibitors have higher specificity for FLT3 8 and a number of them are being evaluated in latephase clinical trials or are under FDA review, including gilteritinib, crenolanib, and quizartinib. 8,18 The introduction of new treatment options are likely to have an impact on treatment patterns that therefore need to be characterized. However, while real-world treatment patterns among patients with AML have been assessed in some claims data studies, these studies mostly focused on elderly patients in the United States and did not differentiate between patients with FLT3 mut AML and FLT3 wild-type AML (FLT3 wt AML).…”

mentioning

confidence: 99%

Treatment patterns and healthcare resource utilization in patients withFLT3‐mutated and wild‐type acute myeloid leukemia: A medical chart study

Griffin

Yang

Song

et al. 2019

European J of Haematology

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ObjectivesTo assess real‐world treatment patterns and healthcare resource utilization (HRU) among patients with FLT3–mutated (FLT3 mut) and FLT3–wild‐type (FLT3 wt) acute myeloid leukemia (AML).MethodsData were abstracted from medical charts of patients with AML from 10 countries. Patients were grouped based on their FLT3 mutation status, age (18‐64 or ≥65), and whether they were newly diagnosed (ND) or relapsed/refractory (R/R).ResultsCharts of 1027 AML patients were included (183 FLT3 mut 18‐64 ND; 136 FLT3 mut ≥65 ND; 181 FLT3 mut R/R; 186 FLT3 wt 18‐64 ND; 159 FLT3 wt ≥65 ND; 182 FLT3 wt R/R). Substantial heterogeneity was observed in treatment patterns for AML. Among ND patients 18‐64, the most common initial treatment was standard‐to‐intermediate dose cytarabine‐based therapies (43.2% for FLT3 mut and 55.9% for FLT3 wt); among ND patients ≥65, the most common initial treatment was hypomethylating agent‐based therapies (36.0% and 47.2%). Among R/R patients, the most common initial treatment after R/R was best supportive care only (39.8% and 24.7%). HRU was substantial across cohorts during both event‐free and post‐event periods.ConclusionsTreatment patterns of AML were heterogeneous and FLT3 mut AML was treated more aggressively than FLT3 wt disease. HRU was substantial for all cohorts, particularly after relapse or treatment failure.

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“…First, dasatinib, a small-molecule multikinase inhibitor used to treat cancer, was selected as a recently approved drug with a target-based rational drug design [39]. Consequently, the observational and interventional side effects clinical data on the drug were relatively abundant, and swift data updates for indication expansion were expected.…”

Section: Case Studiesmentioning

confidence: 99%

Prediction of Side Effects Using Comprehensive Similarity Measures

Seo

Lee

Kim

et al. 2020

BioMed Research International

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Identifying the potential side effects of drugs is crucial in clinical trials in the pharmaceutical industry. e existing side effect prediction methods mainly focus on the chemical and biological properties of drugs. is study proposes a method that uses diverse information such as drug-drug interactions from DrugBank, drug-drug interactions from network, single nucleotide polymorphisms, and side effect anatomical hierarchy as well as chemical structures, indications, and targets. e proposed method is based on the assumption that properties used in drug repositioning studies could be utilized to predict side effects because the phenotypic expression of a side effect is similar to that of the disease. e prediction results using the proposed method showed a 3.5% improvement in the area under the curve (AUC) over that obtained when only chemical, indication, and target features were used. e random forest model delivered outstanding results for all combinations of feature types. Finally, after identifying candidate side effects of drugs using the proposed method, the following four popular drugs were discussed: (1) dasatinib, (2) sitagliptin, (3) vorinostat, and (4) clonidine.

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Protein kinase inhibitors for acute leukemia

Cited by 29 publications

References 78 publications

BCR-AblSilencing by siRNA: A Potent Approach to Sensitize Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitor Therapy

BCR-AblSilencing by siRNA: A Potent Approach to Sensitize Chronic Myeloid Leukemia Cells to Tyrosine Kinase Inhibitor Therapy

Treatment patterns and healthcare resource utilization in patients withFLT3‐mutated and wild‐type acute myeloid leukemia: A medical chart study

Prediction of Side Effects Using Comprehensive Similarity Measures

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