Abstract:
: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.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Di J,Zheng B,Kong Q,Jiang Y,Liu S,Yang Y,Han X,Sheng Y,Zhang Y,Cheng L,Han Jdoi
10.1002/1878-0261.12564subject
Has Abstractpub_date
2019-10-01 00:00:00pages
2259-2277issue
10eissn
1574-7891issn
1878-0261journal_volume
13pub_type
杂志文章abstract::Mouse models of human cancers may provide a valuable resource for the discovery of cancer biomarkers. We have developed a practical strategy for profiling specific proteins in mouse plasma using low-volume sandwich-immunoassays. We used this method to profile the levels of 14 different cytokines, acute-phase reactants...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2007.06.001
更新日期:2007-09-01 00:00:00
abstract::Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment gi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12790
更新日期:2020-09-04 00:00:00
abstract::Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absen...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.09.001
更新日期:2016-12-01 00:00:00
abstract::As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumu...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12756
更新日期:2020-10-01 00:00:00
abstract::Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenes...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12057
更新日期:2017-09-01 00:00:00
abstract::Endocytosis is an important regulator of cell-cell signaling and endocytic trafficking has been increasingly implicated in control of tumor suppression. Recent insights from Drosophila indicate that impairment of multiple trafficking steps which lead to receptor degradation can cause tumor formation in epithelial orga...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12163
更新日期:2018-05-01 00:00:00
abstract:BACKGROUND:The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested. METHODS:We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.08.002
更新日期:2011-12-01 00:00:00
abstract::Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.07.010
更新日期:2016-11-01 00:00:00
abstract::Targeted therapies, including antibodies, are becoming increasingly important in cancer therapy. Important limitations, however, are that not every patient benefits from a specific antibody therapy and that responses could be short-lived due to acquired resistance. In addition, targeted therapies are quite expensive a...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.03.010
更新日期:2014-06-01 00:00:00
abstract::The promise of 'personalized cancer care' with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given tumor-type from patient to patient (inter-patient heterogeneity), and within an individual (intra-patient heterogeneity) as demon...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.09.011
更新日期:2015-05-01 00:00:00
abstract::The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by perform...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.11.002
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.021
更新日期:2016-02-01 00:00:00
abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12888
更新日期:2020-12-18 00:00:00
abstract::The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.03.004
更新日期:2016-06-01 00:00:00
abstract::Autophagy, a well-described cellular mechanism for lysosomal degradation of cytoplasmic content, has emerged as a tumour suppression pathway. Recent evidence indicates that the tumour suppressor function of autophagy is mediated by scavenging of damaged oxidative organelles, thereby preventing accumulation of toxic ox...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.007
更新日期:2009-08-01 00:00:00
abstract::Cigarette smoking is one of the leading risks for lung cancer and is associated with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains undetermined whether and how cigarette smoke affects the therapeutic efficacy of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12193
更新日期:2018-05-01 00:00:00
abstract::Protein inhibitor of activated STAT3 (PIAS3) is an endogenous suppressor of signal transducer and activator of transcription 3 (STAT3) signaling. By directly interacting with phosphorylated STAT3, PIAS3 can block the downstream transcriptional activity of STAT3, which is hyper-activated in various cancers. We previous...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12386
更新日期:2018-12-01 00:00:00
abstract:PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.005
更新日期:2015-04-01 00:00:00
abstract::Triple-negative breast cancer (TNBC) liver metastasis is associated with poor prognosis and low patient survival. It occurs when tumor cells disseminate from primary tumors, circulate in blood/lymph [circulating tumor cells (CTCs)], and acquire distinct characteristics during disease progression toward the metastatic ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12533
更新日期:2019-09-01 00:00:00
abstract:INTRODUCTION:Most analyses of high throughput cancer data represent tumors by "atomistic" single-gene properties. Pathifier, a recently introduced method, characterizes a tumor in terms of "coarse grained" pathway-based variables. METHODS:We applied Pathifier to study a very large dataset of 2000 breast cancer samples...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.04.006
更新日期:2015-08-01 00:00:00
abstract::PKN3 is an AGC-family protein kinase implicated in growth of metastatic prostate cancer cells with phosphoinositide 3-kinase pathway deregulation. The molecular mechanism, however, by which PKN3 contributes to malignant growth and tumorigenesis is not well understood. Using orthotopic mouse tumor models, we now show t...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.12.001
更新日期:2012-06-01 00:00:00
abstract::It is well known that different racial groups have significantly different incidence and mortality rates for certain cancers. It has been suggested that biological factors play a major role in these cancer racial disparities. Previous studies on the biological factors contributing to cancer racial disparity have gener...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12799
更新日期:2020-09-13 00:00:00
abstract:PURPOSE:To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients. PATIENTS AND METHODS:Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00
abstract::Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases, however, their role in tumor biology and as a drug target is not clear. In the present study, a stable neurotensin (NT) analog induced intracellular calcium release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer ce...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2009.01.006
更新日期:2009-06-01 00:00:00
abstract::The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1∆IEC ). Male but not female STAT1∆IEC mi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12178
更新日期:2018-04-01 00:00:00
abstract::Pharmacogenomics is the study of genetic factors determining drug response or toxicity. The use of pharmacogenomics is especially desirable in oncology because the therapeutic index of oncology drugs is often narrow, the need for favorable drug response is often acute, and the consequences of drug toxicity can be life...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2012.01.005
更新日期:2012-04-01 00:00:00
abstract::Prostate cancer (PCa) remains an important public health concern in Western countries. Metabolic syndrome (MeS) is a cluster of pathophysiological disorders with increasing prevalence in the general population that is a risk factor for PCa. Several studies have determined that a crosstalk between white adipose tissue ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12788
更新日期:2020-09-02 00:00:00
abstract::The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tiss...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12487
更新日期:2019-05-01 00:00:00
abstract::The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/i) embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphoma...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.01.001
更新日期:2010-04-01 00:00:00