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Special Issue "Genetic Alterations in Tumors"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 31 January 2022.

Special Issue Editors

Prof. Dr. Giuseppe Damante
E-Mail Website
Guest Editor
1. Department of Medicine, University of Udine, Udine, Italy
2. Institute of Medical Genetics, Academic Hospital of Udine, Udine, Italy
Interests: medical Genetics; genetic diseases; cancer genetics
Dr. Rebecca Chin
E-Mail Website
Guest Editor
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
Interests: signaling pathways perturbed by genetic alterations in human solid tumors

Special Issue Information

Dear Colleagues,

With advances in high-throughput technologies like next-generation sequencing, remarkable progress has been made in understanding genetic events that define the identity of tumors and characterize cancer development and metastasis. Integrative analysis of genomic alterations, signaling, and other molecular changes in tumor cells have allowed not only biomarker discovery, but also the identification of novel therapeutic targets. Personalized cancer therapy based on genetic status has shown great promise for the improvement of patient outcomes. However, many challenges remain, including tumor heterogeneity and therapeutic resistance arising from genetic mutations as compensatory mechanisms. It is also now clear that there are interplays between the genome and epigenome of tumor cells, adding another layer of complexity in our understanding of cancer.

In this Special Issue, we welcome reviews, original research articles, and short communications that focus on advances related to identifying genetic events that improve cancer diagnosis, the development of targeted therapy, combating resistance, as well as genetic events changing the epigenomic landscape of tumor cells.

Prof. Dr. Giuseppe Damante
Dr. Rebecca Chin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Genetic
  • Genomic
  • Gene fusion
  • Breast cancer
  • Metastasis
  • Epigenome
  • Signaling
  • Precision medicine
  • Resistance
  • Patient tailoring

Published Papers (1 paper)

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Research

Article
In-Silico Evaluation of Genetic Alterations in Ovarian Carcinoma and Therapeutic Efficacy of NSC777201, as a Novel Multi-Target Agent for TTK, NEK2, and CDK1
Int. J. Mol. Sci. 2021, 22(11), 5895; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115895 - 31 May 2021
Cited by 1 | Viewed by 953
Abstract
Ovarian cancer is often detected at the advanced stages at the time of initial diagnosis. Early-stage diagnosis is difficult due to its asymptomatic nature, where less than 30% of 5-year survival has been noticed. The underlying molecular events associated with the disease’s pathogenesis [...] Read more.
Ovarian cancer is often detected at the advanced stages at the time of initial diagnosis. Early-stage diagnosis is difficult due to its asymptomatic nature, where less than 30% of 5-year survival has been noticed. The underlying molecular events associated with the disease’s pathogenesis have yet to be fully elucidated. Thus, the identification of prognostic biomarkers as well as developing novel therapeutic agents for targeting these markers become relevant. Herein, we identified 264 differentially expressed genes (DEGs) common in four ovarian cancer datasets (GSE14407, GSE18520, GSE26712, GSE54388), respectively. We constructed a protein-protein interaction (PPI) interaction network with the overexpressed genes (72 genes) and performed gene enrichment analysis. In the PPI networks, three proteins; TTK Protein Kinase (TTK), NIMA Related Kinase 2 (NEK2), and cyclin-dependent kinase (CDK1) with higher node degrees were further evaluated as therapeutic targets for our novel multi-target small molecule NSC777201. We found that the upregulated DEGs were enriched in KEGG and gene ontologies associated with ovarian cancer progression, female gamete association, otic vesicle development, regulation of chromosome segregation, and therapeutic failure. In addition to the PPI network, ingenuity pathway analysis also implicate TTK, NEK2, and CDK1 in the elevated salvage pyrimidine and pyridoxal pathways in ovarian cancer. The TTK, NEK2, and CDK1 are over-expressed, demonstrating a high frequency of genetic alterations, and are associated with poor prognosis of ovarian cancer cohorts. Interestingly, NSC777201 demonstrated anti-proliferative and cytotoxic activities (GI50 = 1.6 µM~1.82 µM and TGI50 = 3.5 µM~3.63 µM) against the NCI panels of ovarian cancer cell lines and exhibited a robust interaction with stronger affinities for TTK, NEK2, and CDK1, than do the standard drug, paclitaxel. NSC777201 displayed desirable properties of a drug-like candidate and thus could be considered as a novel small molecule for treating ovarian carcinoma. Full article
(This article belongs to the Special Issue Genetic Alterations in Tumors)
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