Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma

Saeed, Mohamed E.M.; Kadioglu, Onat; Greten, Henry Johannes; Yıldırım, Adem; Mayr, Katharina; Wenz, Frederik; Giordano, Frank A.; Efferth, Thomas

doi:10.1007/s10637-020-01037-7

Cited by 7 publications

(1 citation statement)

References 64 publications

(70 reference statements)

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“…The idea to exploit immunohistochemical protein expression profiling for targeted tumor therapy is different from a previous approach where we combined RNAsequencing of a glioblastoma patient with a bioinformaticsbased virtual screening of FDA-approved drugs (22). The concept of drug repurposing is based on the observation that…”

Section: Cancer Genomics and Proteomicsmentioning

confidence: 99%

Protein Expression Profiling and Virtual Drug Screening as an Approach for Individualized Therapy of Small Cell Vaginal Carcinoma

Saeed

Khalid

Thakur³

et al. 2022

Cancer Genomics Proteomics

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Background: Small cell vaginal carcinoma is a very rare gynecological cancer and treatments including chemo-and radiotherapy have had limited success. Case Report: We report the case of a 37-year-old female, where intensive treatment with the combination of paclitaxel, carboplatin, irinotecan, and camptothecin with and without irradiation did not avoid metastasis of the tumor and the death of the patient. In an attempt to develop a strategy for individualized tumor therapy, we performed immunohistochemistry of 19 cancer-related proteins using a biopsy sample. Strong expression was observed for glutathione S-transferase P1 (GSTP1), epidermal growth factor receptor (EGFR), inducible nitric oxide synthetase (iNOS), nuclear factor kappa B (NF-ĸB), the oncogene c-MYC, vascular endothelial growth factor (VEGF), and the proliferation marker Ki-67. Intermediate expression was found for the oncogene SRC, β-catenin, and the viral E7 protein. We then performed virtual drug screening with PyRx and molecular docking with AutoDock 4.2.6 by using the three-dimensional structures of these proteins and a chemical library of 1,577 FDA-approved drugs, in a drug repurposing approach. The top 15 compounds were either approved anticancer drugs or drugs used to treat nonmalignant diseases. These compounds were bound with comparable or even higher affinity to the targets compared to control inhibitors. Several of these compounds were bound with high affinity to more than one of these target proteins, further supporting the drug repurposing concept. Conclusion: These drugs might offer additional opportunities to reach treatment responses. This approach of individualized tumor therapy might be theoretically not only applicable for small cell vaginal carcinoma but for other tumor entities as well.

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Section: Cancer Genomics and Proteomicsmentioning

confidence: 99%

Protein Expression Profiling and Virtual Drug Screening as an Approach for Individualized Therapy of Small Cell Vaginal Carcinoma

Saeed

Khalid

Thakur³

et al. 2022

Cancer Genomics Proteomics

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Combination Drug Therapy of Glioblastoma: Lessons from 3D In Vitro Models and the Roadmap for Future Research

Vaezzadeh,

Kachooei,

Krishnamurthy

et al. 2023

Advanced Therapeutics

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Combination drug therapy addresses the auxiliary cancer pathways of the tumor progression unaffected by the standard adjuvant treatments such as radio‐ and chemotherapy. It is a particularly attractive strategy to improve the treatment outcomes and the quality of life in patients with the deadliest brain cancer, glioblastoma (GB). Testing of combination drug treatment protocols requires reliable, efficient, and biologically accurate preclinical testbeds applicable before the transition to clinical trials. The 3D in vitro models of GB are a promising platform for pharmacological research. However, there is notable methodological uncertainty and a highly scattered data landscape regarding drug testing in 3D in vitro models of GB. In particular, it is not completely clear how to mimic clinically relevant dozing and schedule of the main chemotherapy drug for GB, temozolomide (TMZ) in 3D in vitro GB models. Here, the authors carefully explore the available literature on the application of TMZ in 3D in vitro models of GB, both as a sole agent and in combination with other medications. The joint analysis of the tumor modeling approaches, the employed assays, and the obtained treatment responses provided in this review may be used as a roadmap for future research in combination treatments of GB.

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Artesunate/temozolomide

2021

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Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma

Cited by 7 publications

References 64 publications

Protein Expression Profiling and Virtual Drug Screening as an Approach for Individualized Therapy of Small Cell Vaginal Carcinoma

Protein Expression Profiling and Virtual Drug Screening as an Approach for Individualized Therapy of Small Cell Vaginal Carcinoma

Combination Drug Therapy of Glioblastoma: Lessons from 3D In Vitro Models and the Roadmap for Future Research

Artesunate/temozolomide

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