Bruton tyrosine kinase inhibitor ONO/GS-4059: from bench to bedside

Wu, Jingjing; Zhang, Mingzhi; Liu, Delong

doi:10.18632/oncotarget.12786

Cited by 28 publications

(14 citation statements)

References 86 publications

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“…Ono/GS-4059 has been evaluated in DLBCL and MCL cell lines in combination with other agents. Ono and phsophotidylinositol 3 kinase inhibitor idelalisib showed synergistic activity in inhibiting the growth of a subset of these cell lines [ 37 ]. In a phase 1 clinical trial, Ono demonstrated a 92% (11 of 12) overall response rate in patients with MCL [ 38 ].…”

Section: Treatment Of Mantle Cell Lymphomamentioning

confidence: 99%

The B cell receptor signaling pathway in mantle cell lymphoma

et al. 2018

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Signal transduction through the constitutively activated B cell receptor (BCR) plays a key role in the pathogenesis of B-cell tumors by promoting survival and proliferation of malignant B cells. The BCR signaling pathway is known to be deregulated in Mantle Cell Lymphoma (MCL) due to mutations or epigenetic events that impact regulatory proteins. One such protein is Bruton's tyrosine kinase (BTK), an integral component of the BCR signaling pathway. The success of ibrutinib, a BTK inhibitor, and other drugs that target components of the BCR pathway is evidence that regulation of the BCR signaling pathway is an effective method of MCL treatment. The complexity of the pathway indicates that it contains other potential therapeutic targets for the treatment of MCL. This is supported by recent and ongoing clinical trials of inhibitors of molecules such as PI3K, BCL-2, and BTK that show promising initial results. Additionally, agents that target different points of the pathway may have synergistic effects when used in combination. This review provides a description of the BCR signaling pathway on the molecular level followed by an explanation of its relationship to MCL. The role of the BCR signaling pathway in the pathogenesis of MCL is explained through an overview of the drugs that target BCR signaling in MCL treatment.

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Section: Treatment Of Mantle Cell Lymphomamentioning

confidence: 99%

The B cell receptor signaling pathway in mantle cell lymphoma

et al. 2018

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“…11 More selective and potent BTK inhibitors are currently being investigated clinically. 3,12,13 CC 292 is a potent, selective, orally administered small-molecule inhibitor of BTK. CC 292 inhibits BTK activity by binding with high affinity to the adenosine triphosphate binding site of BTK and forming a covalent bond with the target BTK protein, providing rapid, complete, and prolonged inhibition of BTK activity, both in vitro and in vivo.…”

mentioning

confidence: 99%

Population Pharmacokinetics and Exposure Response Assessment of CC‐292, a Potent BTK Inhibitor, in Patients With Chronic Lymphocytic Leukemia

Li¹,

Ramírez‐Valle²,

Xue³

et al. 2017

The Journal of Clinical Pharma

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CC‐292, a potent Bruton tyrosine kinase inhibitor, is under development for the treatment of B‐cell malignancies. An analysis was performed to develop a population pharmacokinetic model of CC‐292 and assess the influence of demographics and disease‐related covariates on CC‐292 exposure and to assess the exposure‐response (overall response rate) relationship in patients with chronic lymphocytic leukemia. Population pharmacokinetic analysis was based on a 2‐compartment base model conducted in NONMEM. Categorical exposure‐response analysis was performed using logistic regression in SAS. The population pharmacokinetic analysis results indicated that CC‐292 pharmacokinetic disposition is similar between healthy subjects and patients. CC‐292 showed a larger central compartment volume of distribution than the peripheral compartment volume of distribution (158 L and 72 L, respectively) and a faster clearance than intercompartmental clearance (134 L/h and 18.7 L/h, respectively), indicating that for CC‐292, clearance from blood occurs faster than distribution into deep tissues and organs. CC‐292 clearance is not affected by demographics or baseline clinical lab factors, except for sex. Although sex significantly reduced variation of apparent clearance, the sex effect on apparent clearance is unlikely to be clinically relevant. The exposure‐response analysis suggested that higher drug exposure is linearly correlated with higher overall response rate. A twice‐daily dose regimen showed higher overall response rate as compared to once‐daily dosing, consistent with a threshold concentration of approximately 300 ng/mL, above which the probability of overall response rate significantly increases.

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“…As mentioned earlier, intratumoral injection of poly I:C slowed tumor progression (Salmon et al, 2016), an effect that may be due to activation of TLR3-expressing CD103 + cDC1s in the TME. In addition, imiquimod, a TLR7 agonist, is an approved therapy for basal cell carcinoma, implicating pDC stimulation and production of IFN-Is as important in anti-tumor activity (Le Mercier et al, 2013;Wu et al, 2017). Others TLR agonists are in clinical trials or have been approved for use in cancer; this topic is covered in greater detail in an earlier review (Shi et al, 2016).…”

Section: Ifn-i-stat1 Tlr and Sting Signaling In Dcs In The Tmementioning

confidence: 99%

“…For example, human pDCs activated by imiquimod or IFN-α, were able to lyse multiple human melanoma cell lines ex vivo (Kalb et al, 2012). Moreover, murine pDCs activated with either imiquimod or CpG (a TLR9 agonist) showed direct cytotoxic effects on mouse breast cancer cells in vitro, and suppressed tumor growth in vivo (Wu et al, 2017). Given the cytotoxic effects of IFN-Is, it is possible these responses result directly from pDC-mediated IFN-I production, although alternative mechanisms may also contribute.…”

Section: Roles For Pdcs In Solid Tumorsmentioning

confidence: 99%

Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer

Chrisikos

Zhou

Slone

et al. 2019

Molecular Immunology

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Dendritic cells (DCs) are the principal antigen-presenting cells of the immune system and play key roles in controlling immune tolerance and activation. As such, DCs are chief mediators of tumor immunity. DCs can regulate tolerogenic immune responses that facilitate unchecked tumor growth. Importantly, however, DCs also mediate immune-stimulatory activity that restrains tumor progression. For instance, emerging evidence indicates the cDC1 subset has important functions in delivering tumor antigens to lymph nodes and inducing antigen-specific lymphocyte responses to tumors. Moreover, DCs control specific therapeutic responses in cancer including those resulting from immune checkpoint blockade. DC generation and function is influenced profoundly by cytokines, as well as their intracellular signaling proteins including STAT transcription factors. Regardless, our understanding of DC regulation in the cytokine-rich tumor microenvironment is still developing and must be better defined to advance cancer treatment. Here, we review literature focused on the molecular control of DCs, with a particular emphasis on cytokine- and STAT-mediated DC regulation. In addition, we highlight recent studies that delineate the importance of DCs in anti-tumor immunity and immune therapy, with the overall goal of improving knowledge of tumor-associated factors and intrinsic DC signaling cascades that influence DC function in cancer.

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Bruton tyrosine kinase inhibitor ONO/GS-4059: from bench to bedside

Cited by 28 publications

References 86 publications

The B cell receptor signaling pathway in mantle cell lymphoma

The B cell receptor signaling pathway in mantle cell lymphoma

Population Pharmacokinetics and Exposure Response Assessment of CC‐292, a Potent BTK Inhibitor, in Patients With Chronic Lymphocytic Leukemia

Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer

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