Cancer/testis antigens as molecular drug targets using network pharmacology
- 265 Downloads
Present chemotherapeutic drugs have limited efficacy and severe side effects. Considering the complexity of cancer, an effective strategy is necessary to discover multiple new drug targets. Cancer/testis antigens are vital for cancer cell progression. We have performed a computational network analysis of cancer/testis antigens and assessed these antigens as drug targets. During this analysis, protein interaction network of 700 human CT antigens was investigated. CT antigen network consisted of eight independent components. Four major hubs and two minor hubs were identified that play nodal role in the flow of information across the largest network. We have predicted 30 potential drug targets by analysing several topological parameters such as betweenness centrality, cluster coefficient and probable protein complexes. Structural and functional roles of potential drug targets have also been anatomized. Analysis of the CT antigen network enables us to pinpoint a set of candidate proteins that if targeted could be detrimental for cancerous cell without affecting any normal cell. The list of putative proteins is a starting point for experimental validation and may help further in the discovery of new anticancer drug targets.
KeywordsCancer Cancer/testis antigens Protein interaction network Anticancer targets
Authors are thankful to SERB, Dept. of Science and Technology (DST), Govt. of India for providing financial assistance to the lab. Authors would also like to acknowledge the help and guidance received by Dr. Vishal Acharya, IHBT, Palampur, while preparing manuscript.
- 5.von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–77.CrossRefPubMedGoogle Scholar
- 12.Peche LY, Ladelfa MF, Toledo MF, Mano M, Laiseca JE, Schneider C, Monte M. Human MageB2 protein expression enhances E2F transcriptional activity, cell proliferation, and resistance to ribotoxic stress. J Biol Chem. 2015;290(49):29652–62. doi: 10.1074/jbc.M115.671982.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Sati L, Zeiss C, Yekkala K, Demir R, McGrath J. Expression of the CTCFL Gene during mouse embryogenesis causes growth retardation, postnatal lethality, and dysregulation of the transforming growth factor beta pathway. Mol Cell Biol. 2015;35(19):3436–45. doi: 10.1128/mcb.00381-15.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Zeidan-Chulia F, Gursoy M, Neves de Oliveira BH, Ozdemir V, Kononen E, Gursoy UK. A systems biology approach to reveal putative host-derived biomarkers of periodontitis by network topology characterization of MMP-REDOX/NO and apoptosis integrated pathways. Front Cell Infect Microbiol. 2015;5:102. doi: 10.3389/fcimb.2015.00102.PubMedGoogle Scholar