scholarly journals Integrative exploration of genomic profiles for triple negative breast cancer identifies potential drug targets

Medicine ◽  
2016 ◽  
Vol 95 (40) ◽  
pp. e6564
Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1724 ◽  
Author(s):  
Maoni Guo ◽  
Siddharth Sinha ◽  
San Ming Wang

Triple-negative breast cancer (TNBC) has poor clinical prognosis. Lack of TNBC-specific biomarkers prevents active clinical intervention. We reasoned that TNBC must have its specific signature due to the lack of three key receptors to distinguish TNBC from other types of breast cancer. We also reasoned that coupling methylation and gene expression as a single unit may increase the specificity for the detected TNBC signatures. We further reasoned that choosing the proper controls may be critical to increasing the sensitivity to identify TNBC-specific signatures. Furthermore, we also considered that specific drugs could target the detected TNBC-specific signatures. We developed a system to identify potential TNBC signatures. It consisted of (1) coupling methylation and expression changes in TNBC to identify the methylation-regulated signature genes for TNBC; (2) using TPBC (triple-positive breast cancer) as the control to detect TNBC-specific signature genes; (3) searching in the drug database to identify those targeting TNBC signature genes. Using this system, we identified 114 genes with both altered methylation and expression, and 356 existing drugs targeting 10 of the 114 genes. Through docking and molecular dynamics simulation, we determined the structural basis between sapropterin, a drug used in the treatment of tetrahydrobiopterin deficiency, and PTGS2, a TNBC signature gene involved in the conversion of arachidonic acid to prostaglandins. Our study reveals the existence of rich TNBC-specific signatures, and many can be drug target and biomarker candidates for clinical applications.


2013 ◽  
Author(s):  
Christof Bernemann ◽  
Carolin Huelsewig ◽  
Marie-Kristin von Wahlde ◽  
Ludwig Kiesel ◽  
Cornelia Liedtke

2007 ◽  
Vol 7 (3) ◽  
pp. 245-251 ◽  
Author(s):  
Marcelo Taborga ◽  
Kelly Corcoran ◽  
Neil Fernandes ◽  
Shakti Ramkissoon ◽  
Pranela Rameshwar

2020 ◽  
Vol 15 (3) ◽  
pp. 242-252
Author(s):  
Abdelmonem M. Abdella ◽  
Mohamedelhafiz Haj ◽  
John E. Scott ◽  
Hagir M. Omer

Author(s):  
Oladoja Awofisayo

Objectives: Diabetes is increasingly recognized as a serious, worldwide public health concern. By early identifying those at risk to develop diabetes and if confirmed to be at pre-diabetes stage adequate care provided for them through lifestyle interventions or even hypoglycemic medications if necessary, thus delaying or preventing their progression to diabetic status. The study aims at assessing the risk of developing type 2 diabetes mellitus (T2DM) among healthy non-diabetic Sudanese in Khartoum city. Breast cancer (BC) is the most common cancer worldwide prevalent among women with more than one million cases and is second only to lung cancer. Methods: The identification of the sequences based on the unique tetramers GCAC, GTCA were selected from experimental work. The16 base pair DNA regulatory sequences of which the motifs area part of containing these motif in genes implicated in cancer CAGE1 (AAGCTGTCATTA), BRCA1(GACTGAGTCAA), ABCB1(CTCTAAGTCAT), ABCB5 (GATATGTTAAAGC) and ABI1(CTTCTGGGAA)  were then selected as novel putative targets in breast cancer therapy based on their selectivity on the BC oncogenes which are not found in the normal human genome 1-23 and the sex chromosomes X and Y were obtained via computational analysis. Results: The single copy base pairs which will be potential drug targets as anticancer drugs were finally obtained as CTGTTATGACTGAGTCAA, CAGE1 with the 17 base pairs CATAAAAGC TGTCATTA and ABCB1 TTGCCAA CTCTAAGT CAT. Conclusion: It is Possible that the in silico discovery of putative anti breast cancer targets of importance in the genome. Peer Review History: Received 18 July 2020; Revised 25 September; Accepted 12 October, Available online 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Nkechi Obiofu Ezenobi, University of Port Harcourt, Nigeria, [email protected] Shahinga Vanji, World Academy of Medical Sciences, Iran,  [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS


2021 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya

: Triple negative breast cancer represents multiple genomic and transcriptomic heterogeneities. Genetic and epigenetic changes emerging in TNBC help it in acquiring resistance against immunological response. Distant metastasis, lack of clinically targeted therapies and prognostic markers make it the most aggressive form of breast cancer. In this review, we showed that driver alterations in targeted genes AR, ERR, TIL, TAM, miRNA, mTOR and immunosuppressive cytokines are predominantly involved in complicating TNBC by inducing cell proliferation, invasion and metastasis, and by inhibiting apoptosis. The role of node status, cathepsin-D, Ki-67 index, CD3+TIL, BRCA1 promoter methylation value and p53 as an efficient prognostic factor have also been studied to predict the disease free and overall survival rate in TNBC patients. The present review article is an attempt to gain an insight with a new vision on the etiology of TNBC, its treatment strategies and prognostic marker to identify the outcome of standard therapies and to re-design future treatment strategies to provide maximum benefit to patients.


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