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A drug repurposing approach for individualized cancer therapy based on transcriptome sequencing and virtual drug screening.
Kadioglu, Onat; Bahramimehr, Faranak; Dawood, Mona; Mahmoud, Nuha; Elbadawi, Mohamed; Lu, Xiaohua; Bülbül, Yagmur; Schulz, Jana Agnieszka; Krämer, Lisa; Urschel, Marie-Kathrin; Künzli, Zoe; Abdulrahman, Leila; Aboumaachar, Fadwa; Kadalo, Lajien; Nguyen, Le Van; Shaidaei, Sara; Thaher, Nawal; Walter, Kathrin; Besler, Karolin Christiane; Spuller, Andreas; Munder, Markus; Greten, Henry Johannes; Efferth, Thomas.
Afiliación
  • Kadioglu O; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Bahramimehr F; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Dawood M; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany; Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum, Sudan.
  • Mahmoud N; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Elbadawi M; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Lu X; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Bülbül Y; Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Schulz JA; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Krämer L; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Urschel MK; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Künzli Z; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Abdulrahman L; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Aboumaachar F; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Kadalo L; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Nguyen LV; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Shaidaei S; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Thaher N; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Walter K; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Besler KC; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • Spuller A; Clinic for Gynecology and Obstetrics, Karlsruhe, Germany.
  • Munder M; Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Greten HJ; Heidelberg Clinic of Integrative Diagnostics, Heidelberg, Germany.
  • Efferth T; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany. Electronic address: efferth@uni-mainz.de.
Comput Biol Med ; 157: 106781, 2023 05.
Article en En | MEDLINE | ID: mdl-36931205
RNA-sequencing has been proposed as a valuable technique to develop individualized therapy concepts for cancer patients based on their tumor-specific mutational profiles. Here, we aimed to identify drugs and inhibitors in an individualized therapy-based drug repurposing approach focusing on missense mutations for 35 biopsies of cancer patients. The missense mutations belonged to 9 categories (ABC transporter, apoptosis, angiogenesis, cell cycle, DNA damage, kinase, protease, transcription factor, tumor suppressor). The highest percentages of missense mutations were observed in transcription factor genes. The mutational profiles of all 35 tumors were subjected to hierarchical heatmap clustering. All 7 leukemia biopsies clustered together and were separated from solid tumors. Based on these individual mutation profiles, two strategies for the identification of possible drug candidates were applied: Firstly, virtual screening of FDA-approved drugs based on the protein structures carrying particular missense mutations. Secondly, we mined the Drug Gene Interaction (DGI) database (https://www.dgidb.org/) to identify approved or experimental inhibitors for missense mutated proteins in our dataset of 35 tumors. In conclusion, our approach based on virtual drug screening of FDA-approved drugs and DGI-based inhibitor selection may provide new, individual treatment options for patients with otherwise refractory tumors that do not respond anymore to standard chemotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transcriptoma / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Comput Biol Med Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transcriptoma / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Comput Biol Med Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos