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Discovery of drug t...
Discovery of drug targets and therapeutic agents based on drug repositioning to treat lung adenocarcinoma
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- Graves, Occam Kelly (författare)
- Harvey Mudd Coll, Claremont, CA 91711 USA.
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- Kim, Woonghee (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Ozcan, Mehmet (författare)
- KTH,Science for Life Laboratory, SciLifeLab
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- Ashraf, Sajda (författare)
- Trustlife Labs, Drug Res & Dev Ctr, TR-34774 Istanbul, Turkiye.
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- Turkez, Hasan (författare)
- Trustlife Labs, Drug Res & Dev Ctr, TR-34774 Istanbul, Turkiye.
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- Yuan, Meng (författare)
- KTH,Science for Life Laboratory, SciLifeLab
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- Zhang, Cheng (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Mardinoglu, Adil (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
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- Li, Xiangyu (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab,Bash Biotech Inc, 600 West Broadway,Suite 700, San Diego, CA 92101 USA.;Guangzhou Lab, Guangzhou 510005, Peoples R China.
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Harvey Mudd Coll, Claremont, CA 91711 USA Systembiologi (creator_code:org_t)
- Elsevier BV, 2023
- 2023
- Engelska.
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier BV. - 0753-3322 .- 1950-6007. ; 161
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Lung adenocarcinoma (LUAD) is the one of the most common subtypes in lung cancer. Although various targeted therapies have been used in the clinical practice, the 5-year overall survival rate of patients is still low. Thus, it is urgent to identify new therapeutic targets and develop new drugs for the treatment of the LUAD patients. Methods: Survival analysis was used to identify the prognostic genes. Gene co-expression network analysis was used to identify the hub genes driving the tumor development. A profile-based drug repositioning approach was used to repurpose the potentially useful drugs for targeting the hub genes. MTT and LDH assay were used to measure the cell viability and drug cytotoxicity, respectively. Western blot was used to detect the expression of the proteins. Findings: We identified 341 consistent prognostic genes from two independent LUAD cohorts, whose high expression was associated with poor survival outcomes of patients. Among them, eight genes were identified as hub genes due to their high centrality in the key functional modules in the gene-co-expression network analysis and these genes were associated with the various hallmarks of cancer (e.g., DNA replication and cell cycle). We performed drug repositioning analysis for three of the eight genes (CDCA8, MCM6, and TTK) based on our drug repositioning approach. Finally, we repurposed five drugs for inhibiting the protein expression level of each target gene and validated the drug efficacy by performing in vitro experiments. Interpretation: We found the consensus targetable genes for the treatment of LUAD patients with different races and geographic characteristics. We also proved the feasibility of our drug repositioning approach for the development of new drugs for disease treatment.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Lung adenocarcinoma
- Co-expression network
- Target identification
- Drug repositioning
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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