From GWAS to drug screening: repurposing antipsychotics for glioblastoma

Lin, Wei-Zhi; Liu, Yen-Chun; Lee, Meng-Chang; Tang, Chi‐Tun; Wu, Gwo-Jang; Chang, Yu-Tien; Chu, Chi‐Ming; Shiau, Chia‐Yang

doi:10.1186/s12967-021-03209-2

Cited by 14 publications

(6 citation statements)

References 79 publications

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“…While the majority of publications (43%) utilized computational techniques to target cancer broadly, including identifying inhibitors ( Brewer et al, 2014 ; Zhong et al, 2015 ; Shafique et al, 2016 ; Ulfa et al, 2017 ; Çınaroğlu and Timuçin, 2019 ; Siam et al, 2020 ), agonists ( Kaur et al, 2015 ; Wang et al, 2018 ), Drug-Target interaction predictions ( Emig et al, 2013 ; Kuthuru et al, 2019 ), and virtual screening ( Rocca et al, 2016 ; Spiliotopoulos et al, 2017b ; Lagarde et al, 2018 ), a portion of the literature concentrated on specific cancer types. Among these, breast cancer (12%) ( Emig et al, 2013 ; Jiang et al, 2017 ; Montes-Grajales et al, 2018 ; Velázquez-Quesada et al, 2020 ; Chequin et al, 2021 ), lymphomas and leukemias (9%) ( Lara-Castillo et al, 2016 ; Sohraby et al, 2017 ; Karube et al, 2018 ; Sahrawat and Kaur, 2019 ; Boulos et al, 2021 ; Parcha et al, 2021 ), lung (6%) ( Kwon et al, 2020 ; Saranyadevi, 2021 ), colorectal (5%) ( Liñares-Blanco et al, 2020 ; Biswas et al, 2021 ; Deokar and Shaikh, 2022 ; Leung et al, 2022 ), and prostate (4%) ( Kang et al, 2018 ; Ariey-Bonnet et al, 2020 ; Benavides-Serrato et al, 2020 ; Liu et al, 2021 ; Lin et al, 2022 ) cancers were the most frequently investigated ( Figure 3B ).…”

Section: Resultsmentioning

confidence: 99%

In silico approaches for drug repurposing in oncology: a scoping review

Cavalcante,

Freitas,

Siquara da Rocha

et al. 2024

Front. Pharmacol.

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Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology.Methods: The scoping review was conducted according to the Arksey and O’Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021.Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies.Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

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Section: Resultsmentioning

confidence: 99%

In silico approaches for drug repurposing in oncology: a scoping review

Cavalcante,

Freitas,

Siquara da Rocha

et al. 2024

Front. Pharmacol.

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“…These studies meticulously scan the vast expanse of our genetic landscape, revealing cryptic variants intricately tied to various diseases [26]. This genetic treasure map marks the first step in the intricate dance of drug discovery and repurposing, as these variants become beacons guiding researchers towards uncharted territories of potential treatments [27]. So, genome-wide association studies (GWAS) play a crucial role in drug repurposing by uncovering genetic variants associated with diseases and providing insights into potential therapeutic targets [28].…”

Section: Gwas and Drug Repurposingmentioning

confidence: 99%

Genomic Approaches for Drug Repurposing

Dave,

Sharma,

Patel

et al. 2024

Preprint

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Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

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“…Genome-wide association studies (GWAS) have also been used to highlight genetic variants associated with certain diseases, and therefore potential therapeutic targets [ 42 ]. A repurposed drug may then be investigated for the treatment of the disease if it is known to target the protein or pathway identified in the GWAS.…”

Section: Repurposed Drugsmentioning

confidence: 99%

“…A recent study by Lin et. al., identified the anti-psychotic imipramine for the treatment of glioblastoma (GB) using this method [ 42 ]. They found that imipramine-targeted GB cells have a higher sensitivity than to temozolomide (TMZ), the current standard chemotherapy for this tumour.…”

Section: Repurposed Drugsmentioning

confidence: 99%

Unlocking hidden potential: advancements, approaches, and obstacles in repurposing drugs for cancer therapy

Weth,

Hoggarth,

Weth

et al. 2023

Br J Cancer

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High rates of failure, exorbitant costs, and the sluggish pace of new drug discovery and development have led to a growing interest in repurposing “old” drugs to treat both common and rare diseases, particularly cancer. Cancer, a complex and heterogeneous disease, often necessitates a combination of different treatment modalities to achieve optimal outcomes. The intrinsic polygenicity of cancer, intricate biological signalling networks, and feedback loops make the inhibition of a single target frequently insufficient for achieving the desired therapeutic impact. As a result, addressing these complex or “smart” malignancies demands equally sophisticated treatment strategies. Combinatory treatments that target the multifaceted oncogenic signalling network hold immense promise. Repurposed drugs offer a potential solution to this challenge, harnessing known compounds for new indications. By avoiding the prohibitive costs and long development timelines associated with novel cancer drugs, this approach holds the potential to usher in more effective, efficient, and cost-effective cancer treatments. The pursuit of combinatory therapies through drug repurposing may hold the key to achieving superior outcomes for cancer patients. However, drug repurposing faces significant commercial, technological and regulatory challenges that need to be addressed. This review explores the diverse approaches employed in drug repurposing, delves into the challenges faced by the drug repurposing community, and presents innovative solutions to overcome these obstacles. By emphasising the significance of combinatory treatments within the context of drug repurposing, we aim to unlock the full potential of this approach for enhancing cancer therapy.

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From GWAS to drug screening: repurposing antipsychotics for glioblastoma

Cited by 14 publications

References 79 publications

In silico approaches for drug repurposing in oncology: a scoping review

In silico approaches for drug repurposing in oncology: a scoping review

Genomic Approaches for Drug Repurposing

Unlocking hidden potential: advancements, approaches, and obstacles in repurposing drugs for cancer therapy

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