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

Di, Jieyi; Zheng, Buhong; Kong, Qingfei; Jiang, Ying; Liu, Siyao; Yang, Yang; Han, Xudong; Sheng, Yuqi; Zhang, Yunpeng; Liang, Cheng; Han, Junwei

doi:10.1002/1878-0261.12564

Cited by 26 publications

(23 citation statements)

References 56 publications

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“…As the development of new cancer drugs is slow and costly, Di et al [38] generated a novel computational approach in order to determine candidate drugs that could possibly be repurposed to treat cancer. By using known drug-indication correlations and combining them with drug-drug and indication-indication similarities, they were subsequently able to hypothesize new drug-indication associations.…”

Section: Breast Cancermentioning

confidence: 99%

“…The algorithm then identified 14 candidate drugs that were statistically significant. In this list of prioritized scores, ibrutinib ranked 3rd out of more than 3000 substances tested and was "considered to show great potential therapeutic effects" [38]. Moreover, ranks 1 and 2 (gefitinib and afatinib) represented two EGFR inhibitors, additional proof of the importance of this receptor in breast cancer treatment.…”

Section: Breast Cancermentioning

confidence: 99%

“…The drug-drug functional similarity network created by Di et al [38] has been described in detail in in Section 2.2.1 above. Even though ibrutinib achieved a high score as a potential agent for breast cancer treatment, it failed to thrive in the experiments on ovarian cancer and ranged in the last sextile of the candidate drug list ranking.…”

Section: Gynecological Malignanciesmentioning

confidence: 99%

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Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review

Metzler

Burla

Fink

et al. 2020

IJMS

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Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton’s tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib’s efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.

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Section: Breast Cancermentioning

confidence: 99%

Section: Breast Cancermentioning

confidence: 99%

Section: Gynecological Malignanciesmentioning

confidence: 99%

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Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review

Metzler

Burla

Fink

et al. 2020

IJMS

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“…For example, Huang et al (2017) identified some hub genes of prostate cancer through an integrated bioinformatics approach and Foj and Filella (2019) identified of potential miRNAs biomarkers for high-grade prostate cancer by integrated bioinformatics analysis. As a matter of fact, the development of bioinformatics technology had not only made great achievements in disease mechanism research and diagnosis and treatment ( Han et al, 2018 ; Zhang et al, 2020 ), but also provided new concepts and means in the way of finding new drug action targets and the preparation process, which greatly promoted the pace of medical research and development from both theoretical and technical aspects ( Du et al, 2018 ; Di et al, 2019 ; Sun et al, 2019 ; Wu et al, 2019 ; Cheng et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Silybin Prevents Prostate Cancer by Inhibited the ALDH1A1 Expression in the Retinol Metabolism Pathway

Jiang

Song

Jiang

et al. 2020

Front. Cell Dev. Biol.

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Background Silybin was known to exert inhibition in prostate cancer, but the underlying mechanism remained largely unknown. This study was designed to find out the potential target of Silybin on prostate cancer and explore the relative mechanisms. Methods Firstly, we screened the possible targets of Silybin through the PubChem database and Subpathway – GM. Then DU145 cells were transferred to investigate the correction about related targets, magnetic bead sorting and flow cytometry were used to sort and identify the cells. Proliferation, migration and invasion ability of DU145 cells were detected by MTT assay, Transwell assay, plate clonality and sphere formation assay. BALB/c nude mice were constructed models with implanted sarcoma and measured the tumor volume every 5 days as wells tumor weight. The levels of proteins were detected by Western blot and immunocytochemistry. RT-PCR was selected to test the expression of protein’s mRNA. Results It was screened out the ALDH1A1 was highly correlated with subpathways of the Silybin risk metabolic pathway. And ALDH1A1 expression was positively correlated RARα with Ets1 by interfering with the ALDH1A1 gene. Importantly, ALDH1A1(+) cells showed proliferation, migration and invasion ability. In addition, it showed that Silybin exerted the inhibition on prostate cells by suppressed the proliferation, migration and invasion ability of cells in vitro experiment. Silybin also reduced the tumor volume and weight. And Silybin displayed obviously reduced the proteins and mRNA of ALDH1A1, RARα, Ets1 and MMP9 expressions. Conclusion Our results indicated that Silybin showed inhibition of prostate cancer and the mechanism was involving with downregulating ALDH1A1 expression, thereby inhibiting the activation of RARα and preventing the activation of Ets1 to inhibit the growth and invasion of prostate cancer.

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“…Subpathways are defined as local gene subregions within canonical biological pathways, and their dysfunction has been reported to be associated with the occurrence, development, and prognosis of cancer (12)(13)(14). Subpathways are also used as signature, biomarkers, and drug recognition of cancer (13,15,16).…”

Section: Introductionmentioning

confidence: 99%

Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme

et al. 2020

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Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant form of glioma and represents 81% of malignant brain and central nervous system (CNS) tumors. Like most cancers, GBM causes metabolic recombination to promote cell survival, proliferation, and invasion of cancer cells. In this study, we propose a method for constructing the metabolic subpathway activity score matrix to accurately identify abnormal targets of GBM metabolism. By integrating gene expression data from different sequencing methods, our method identified 25 metabolic subpathways that were significantly abnormal in the GBM patient population, and most of these subpathways have been reported to have an effect on GBM. Through the analysis of 25 GBM-related metabolic subpathways, we found that (S)-2,3-Epoxysqualene, which was at the central region of the sterol biosynthesis subpathway, may have a greater impact on the entire pathway, suggesting a potential high association with GBM. Analysis of CCK8 cell activity indicated that (S)-2,3-Epoxysqualene can indeed inhibit the activity of U87-MG cells. By flow cytometry, we demonstrated that (S)-2,3-Epoxysqualene not only arrested the U87-MG cell cycle in the G0/G1 phase but also induced cell apoptosis. These results confirm the reliability of our proposed metabolic subpathway identification method and suggest that (S)-2,3-Epoxysqualene has potential therapeutic value for GBM. In order to make the method more broadly applicable, we have developed an R system package crmSubpathway to perform disease-related metabolic subpathway identification and it is freely available on the GitHub ( https://github.com/hanjunwei-lab/crmSubpathway ).

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

Cited by 26 publications

References 56 publications

Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review

Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review

Silybin Prevents Prostate Cancer by Inhibited the ALDH1A1 Expression in the Retinol Metabolism Pathway

Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme

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