Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth

Kinoshita, Taisei; Sukbuntherng, Juthamas; Chang, Betty; Elias, Laurence

doi:10.1158/1535-7163.mct-15-0923

Cited by 76 publications

(67 citation statements)

References 33 publications

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“…These therapeutic strategies may extend beyond B-cell malignancies. Ibrutinib was shown to have activity in several pre-clinical models of solid tumors such as pancreatic cancer [88], breast cancer [89] or lung cancer [90]. Ongoing clinical trials investigate the use of ibrutinib as an immunomodulator alone or in combination with PD-1/PD-L1 inhibitors in solid malignancies [91].…”

Section: Discussionmentioning

confidence: 99%

Harnessing the Effects of BTKi on T Cells for Effective Immunotherapy against CLL

Mhibik¹,

Wiestner²,

Sun³

2019

IJMS

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B-cell receptor (BCR) signaling and tumor–microenvironment crosstalk both drive chronic lymphocytic leukemia (CLL) pathogenesis. Within the microenvironment, tumor cells shape the T-cell compartment, which in turn supports tumor growth and survival. Targeting BCR signaling using Bruton tyrosine kinase inhibitors (BTKi) has become a highly successful treatment modality for CLL. Ibrutinib, the first-in-class BTKi, also inhibits Tec family kinases such as interleukin-2–inducible kinase (ITK), a proximal member of the T-cell receptor signaling cascade. It is increasingly recognized that ibrutinib modulates the T-cell compartment of patients with CLL. Understanding these T-cell changes is important for immunotherapy-based approaches aiming to increase the depth of response and to prevent or treat the emergence of resistant disease. Ibrutinib has been shown to improve T-cell function in CLL, resulting in the expansion of memory T cells, Th1 polarization, reduced expression of inhibitory receptors and improved immune synapse formation between T cells and CLL cells. Investigating the modulation of BTKi on the T-cell antitumoral function, and having a more complete understanding of changes in T cell behavior and function during treatment with BTKi therapy will inform the design of immunotherapy-based combination approaches and increase the efficacy of CLL therapy.

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Section: Discussionmentioning

confidence: 99%

Harnessing the Effects of BTKi on T Cells for Effective Immunotherapy against CLL

Mhibik¹,

Wiestner²,

Sun³

2019

IJMS

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“…Ibrutinib has shown anti-tumor effects towards chronic lyphocytic leukemia [20][21][22][23]. It also shown growth inhibitory effect in solid cancers, but the results is limited [24][25][26][27]. Based on these, a series of derivatives are obtained.…”

Section: Discussionmentioning

confidence: 99%

The Ibr-7 Derivative of Ibrutinib Exhibits Radiosensitivity in Pancreatic Cancer Cells via Targeting EGFR

Tan¹,

Zhang²,

Yan

et al. 2020

Preprint

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Background: Radiotherapy is one of the main therapeutic methods for pancreatic cancer, but radiation resistance limits the clinical application. As a result, novel therapeutic agents to improve the radiosensitivity is urgent. This study aimed to investigate the effect of Ibr-7 (the derivative of ibrutinib) on radiosensitivity of human pancreatic cancer cells.Methods: The effect of Ibr-7 on pancreatic cancer cell’s proliferation were detected by CCK-8 assay. Radiosensitivity was assessed by clonogenic formation assay. Cell cycle, cell apoptosis were analyzed by flow cytometry. DNA damage was detected by immunofluorescence analysis. The expression of p-EGFR, EGFR were determined by western blot.Results: Ibr-7 showed anti-proliferative effect in PANC-1 and Capan2 cells in a dose- and time-dependent manner. Ibr-7 (2 µmol/L) enhanced the effect of radiation in PANC-1 and Capan2 cells. Further findings showed that this combination enhanced G2/M phase arrest and increased cell apoptosis. Additional molecular mechanism studies revealed that the expression of p-EGFR was decreased by Ibr-7 alone or combined with radiation. Overexpression of EGFR reversed the cell apoptosis induced by Ibr-7 combined with radiation. Moreover, the expression of γ-H2AX was significantly decreased in Ibr-7 combined with radiation group.Conclusions: Our study indicated that the potential application of Ibr-7 as a highly effective radiosensitizer for the treatment of pancreatic cancer cells.

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“…Ibrutinib has been reported to play a valuable role in inhibiting activity of BTK-C, a novel isoform of BTK that protects breast cancer cells from apoptosis (Wang et al, 2016). Specifically, the effect of ibrutinib has been clearly confirmed in the suppression of the growth of HER2+ breast cancer cell lines (Chen et al, 2016). Thus, it could become a drug for the treatment of ErbB2+ breast cancer (Campbell et al, 2018;Grabinski and Ewald, 2014).…”

Section: Prioritization Of Drugs For Breast Cancermentioning

confidence: 99%

Prioritization of candidate cancer drugs based on a drug functional similarity network constructed by integrating pathway activities and drug activities

Zheng

Kong

et al. 2019

Molecular Oncology

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Due to the speed, efficiency, relative risk, and lower costs compared to traditional drug discovery, the prioritization of candidate drugs for repurposing against cancers of interest has attracted the attention of experts in recent years. Herein, we present a powerful computational approach, termed prioritization of candidate drugs (PriorCD), for the prioritization of candidate cancer drugs based on a global network propagation algorithm and a drug–drug functional similarity network constructed by integrating pathway activity profiles and drug activity profiles. This provides a new approach to drug repurposing by first considering the drug functional similarities at the pathway level. The performance of PriorCD in drug repurposing was evaluated by using drug datasets of breast cancer and ovarian cancer. Cross‐validation tests on the drugs approved for the treatment of these cancers indicated that our approach can achieve area under receiver‐operating characteristic curve (AUROC) values greater than 0.82. Furthermore, literature searches validated our results, and comparison with other classical gene‐based repurposing methods indicated that our pathway‐level PriorCD is comparatively more effective at prioritizing candidate drugs with similar therapeutic effects. We hope that our study will be of benefit to the field of drug discovery. In order to expand the usage of PriorCD, a freely available R‐based package, PriorCD, has been developed to prioritize candidate anticancer drugs for drug repurposing.

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Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth

Cited by 76 publications

References 33 publications

Harnessing the Effects of BTKi on T Cells for Effective Immunotherapy against CLL

Harnessing the Effects of BTKi on T Cells for Effective Immunotherapy against CLL

The Ibr-7 Derivative of Ibrutinib Exhibits Radiosensitivity in Pancreatic Cancer Cells via Targeting EGFR

Prioritization of candidate cancer drugs based on a drug functional similarity network constructed by integrating pathway activities and drug activities

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