Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK positive neuroblastoma cells, Drosophila and mice

Siaw, Joachim Tetteh

doi:10.1016/s0959-8049(16)61521-6

Cited by 9 publications

(17 citation statements)

References 36 publications

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“… The table is compiled from three independent articles, all of which have employed investigated crizotinib for comparison with other ALK TKIs . Crizotinib* indicates average of crizotinib treatment based on these studies and crizo* SD indicates standard deviation of these values.…”

Section: Targeting Alk In Neuroblastomamentioning

confidence: 99%

“…A number of studies have investigated the effect of ALK TKIs in a neuroblastoma setting (86,87,90,120,132,139,140,146,147). Table 2 shows a selection of FDA approved ALK TKIs, brigatinib, ceritinib, lorlatinib and crizotinib (120,132,140), that vary in their efficacy to inhibit the different ALK mutant variants observed in neuroblastoma in preclinical models. Although not performed side-byside, the accumulated results illustrate potential differences, important as the different ALK TKIs bind differentially within the ATP-binding pocket of the ALK kinase domain (Fig.…”

Section: Targeting Alk In Neuroblastomamentioning

confidence: 99%

“…Efforts are currently being concentrated on understanding how ALK TKIs can be employed therapeutically in combination so in the future patients are treated accordingly. (120,132,140). Crizotinib* indicates average of crizotinib treatment based on these studies and crizo* SD indicates standard deviation of these values.…”

Section: Combinatorial Treatments In Neuroblastomamentioning

confidence: 99%

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Targeting anaplastic lymphoma kinase in neuroblastoma

Umapathy

Mendoza-García

Hållberg

et al. 2019

APMIS

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Over the last decade, anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase (RTK), has been identified as a fusion partner in a diverse variety of translocation events resulting in oncogenic signaling in many different cancer types. In tumors where the full‐length ALK RTK itself is mutated, such as neuroblastoma, the picture regarding the role of ALK as an oncogenic driver is less clear. Neuroblastoma is a complex and heterogeneous tumor that arises from the neural crest derived peripheral nervous system. Although high‐risk neuroblastoma is rare, it often relapses and becomes refractory to treatment. Thus, neuroblastoma accounts for 10–15% of all childhood cancer deaths. Since most cases are in children under the age of 2, understanding the role and regulation of ALK during neural crest development is an important goal in addressing neuroblastoma tumorigenesis. An impressive array of tyrosine kinase inhibitors (TKIs) that act to inhibit ALK have been FDA approved for use in ALK‐driven cancers. ALK TKIs bind differently within the ATP‐binding pocket of the ALK kinase domain and have been associated with different resistance mutations within ALK itself that arise in response to therapeutic use, particularly in ALK‐fusion positive non‐small cell lung cancer (NSCLC). This patient population has highlighted the importance of considering the relevant ALK TKI to be used for a given ALK mutant variant. In this review, we discuss ALK in neuroblastoma, as well as the use of ALK TKIs and other strategies to inhibit tumor growth. Current efforts combining novel approaches and increasing our understanding of the oncogenic role of ALK in neuroblastoma are aimed at improving the efficacy of ALK TKIs as precision medicine options in the clinic.

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Section: Targeting Alk In Neuroblastomamentioning

confidence: 99%

Section: Targeting Alk In Neuroblastomamentioning

confidence: 99%

Section: Combinatorial Treatments In Neuroblastomamentioning

confidence: 99%

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Targeting anaplastic lymphoma kinase in neuroblastoma

Umapathy

Mendoza-García

Hållberg

et al. 2019

APMIS

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“…ALK is a kind of orphan receptor tyrosine kinase (RTK) normally expressed only in the developing nervous system. Point mutations in ALK occur as primary driver mutations in therapy naive patients . Several in vivo resistance mutations in ALK, such as L1196M, C1156Y, F1174L, L1152R, G1269A, and R1275Q have been detected recently.…”

Section: Introductionmentioning

confidence: 99%

Molecular inhibitory mechanism study on the potent inhibitor brigatinib against four crizotinib‐resistant ALK mutations

Song

Liu

et al. 2018

J of Cellular Biochemistry

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As a potent and selective drug, brigatinib exhibits high efficacy against wild-type and mutant anaplastic lymphoma kinase (ALK) proteins to treat non-small cell lung cancer. In this work, the mechanisms of brigatinib binding to wild type and four mutant ALKs were investigated to gain insight into the dynamic energetic and structural information with respect to the design of novel inhibitors. Comparison between ALK-brigatinib and ALK-crizotinib suggests that the scaffold of brigatinib is well anchored to the residue Met1199 of hinge region by two hydrogen bonds, and the residue Lys1150 has the strong electrostatic interaction with the dimethylphosphine oxide moiety in brigatinib. These ALK mutations have significant influences on the flexibility of P-loop region and DFG sequences, but do not impair the hydrogen bonds between brigatinib and the residue Met1199 of hinge region. And mutations (L1196M, G1269A, F1174L, and R1275Q) induce diverse conformational changes of brigatinib and the obvious energy variation of residues Glu1167, Arg1209, Asp1270, and Asp1203. Together, the detailed explanation of mechanisms of those mutations with brigatinib further provide several guidelines for the development of more effective ALK inhibitors.

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“…Alectinib (Alecensa, Hoffmann-La Roche Inc.) [40,41] was approved in 2015 for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. Brigatinib (Alunbrig, ARIAD Pharmaceuticals, Inc.) [3,42] was approved in 2017 for the treatment of patients with metastatic ALK-positive NSCLC who have progressed on or are intolerant to crizotinib.…”

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confidence: 99%

A decade of targeted therapy for non-small cell lung cancer

Ajaj¹

2017

J Pulmonol Respir Res

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Chemotherapy is one of the main treatment options for cancer. However, chemotherapeutic agents usually suffer from poor pharmaceutical properties that restrict their use. Targeted therapy drugs have been developed to specifi cally target changes in cancer cells that help these cells to grow. Such drugs often work when standard chemotherapeutic drugs do not, they often have less severe side effects and they are most often used for advanced cancers. The objective of this article is to give an overview about the 16 FDA-approved targeted therapy drugs to treat non-small cell lung cancer. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Subtypes of NSCLC include squamous cell carcinoma, adenocarcinoma, large cell carcinoma and the less common adenosquamos carcinoma and sarcomatoid carcinoma. MiniMany factors increase the risk for NSCLC such as smoking, genetic factors, exposure to radon gas, asbestos, second-hand smoke, or other forms of air pollution.Signs or symptoms are usually not observed in the early stages of lung cancer, but many signs of eventually developed NSCLC include persistent cough, coughing up blood, persistent breathlessness, unexplained tiredness and weight loss, and an ache or pain when breathing or coughing.Diagnosis of NSCLC can be achieved with different methods such as chest radiographs and computed tomography (CT) scans, which can be con irmed by biopsy that is usually performed by bronchoscopy or CT-guidance.

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Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK positive neuroblastoma cells, Drosophila and mice

Cited by 9 publications

References 36 publications

Targeting anaplastic lymphoma kinase in neuroblastoma

Targeting anaplastic lymphoma kinase in neuroblastoma

Molecular inhibitory mechanism study on the potent inhibitor brigatinib against four crizotinib‐resistant ALK mutations

A decade of targeted therapy for non-small cell lung cancer

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