Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies
Cancer is a complex disease whereby multiple genetic aberrations, epigenetic modifications, metabolic reprogramming, and the microenvironment contribute to the development of a tumor. In the traditional anticancer drug discovery pipeline, drug candidates are usually screened in vitro using two-dimen...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.949241/full |
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| author | Chamoné Munnik Malungi P. Xaba Sibusiso T. Malindisa Bonnie L. Russell Bonnie L. Russell Selisha A. Sooklal |
| author_facet | Chamoné Munnik Malungi P. Xaba Sibusiso T. Malindisa Bonnie L. Russell Bonnie L. Russell Selisha A. Sooklal |
| author_sort | Chamoné Munnik |
| collection | DOAJ |
| description | Cancer is a complex disease whereby multiple genetic aberrations, epigenetic modifications, metabolic reprogramming, and the microenvironment contribute to the development of a tumor. In the traditional anticancer drug discovery pipeline, drug candidates are usually screened in vitro using two-dimensional or three-dimensional cell culture. However, these methods fail to accurately mimic the human disease state. This has led to the poor success rate of anticancer drugs in the preclinical stages since many drugs are abandoned due to inefficacy or toxicity when transitioned to whole-organism models. The common fruit fly, Drosophila melanogaster, has emerged as a beneficial system for modeling human cancers. Decades of fundamental research have shown the evolutionary conservation of key genes and signaling pathways between flies and humans. Moreover, Drosophila has a lower genetic redundancy in comparison to mammals. These factors, in addition to the advancement of genetic toolkits for manipulating gene expression, allow for the generation of complex Drosophila genotypes and phenotypes. Numerous studies have successfully created Drosophila models for colorectal, lung, thyroid, and brain cancers. These models were utilized in the high-throughput screening of FDA-approved drugs which led to the identification of several compounds capable of reducing proliferation and rescuing phenotypes. More noteworthy, Drosophila has also unlocked the potential for personalized therapies. Drosophila ‘avatars’ presenting the same mutations as a patient are used to screen multiple therapeutic agents targeting multiple pathways to find the most appropriate combination of drugs. The outcomes of these studies have translated to significant responses in patients with adenoid cystic carcinoma and metastatic colorectal cancers. Despite not being widely utilized, the concept of in vivo screening of drugs in Drosophila is making significant contributions to the current drug discovery pipeline. In this review, we discuss the application of Drosophila as a platform in anticancer drug discovery; with special focus on the cancer models that have been generated, drug libraries that have been screened and the status of personalized therapies. In addition, we elaborate on the biological and technical limitations of this system. |
| first_indexed | 2024-04-13T19:58:56Z |
| format | Article |
| id | doaj.art-303674583935479ba5bed919dd11ced5 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T19:58:56Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-303674583935479ba5bed919dd11ced52022-12-22T02:32:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.949241949241Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapiesChamoné Munnik0Malungi P. Xaba1Sibusiso T. Malindisa2Bonnie L. Russell3Bonnie L. Russell4Selisha A. Sooklal5Department of Life and Consumer Sciences, University of South Africa, Pretoria, South AfricaDepartment of Life and Consumer Sciences, University of South Africa, Pretoria, South AfricaDepartment of Life and Consumer Sciences, University of South Africa, Pretoria, South AfricaDepartment of Life and Consumer Sciences, University of South Africa, Pretoria, South AfricaBuboo (Pty) Ltd, The Innovation Hub, Pretoria, South AfricaDepartment of Life and Consumer Sciences, University of South Africa, Pretoria, South AfricaCancer is a complex disease whereby multiple genetic aberrations, epigenetic modifications, metabolic reprogramming, and the microenvironment contribute to the development of a tumor. In the traditional anticancer drug discovery pipeline, drug candidates are usually screened in vitro using two-dimensional or three-dimensional cell culture. However, these methods fail to accurately mimic the human disease state. This has led to the poor success rate of anticancer drugs in the preclinical stages since many drugs are abandoned due to inefficacy or toxicity when transitioned to whole-organism models. The common fruit fly, Drosophila melanogaster, has emerged as a beneficial system for modeling human cancers. Decades of fundamental research have shown the evolutionary conservation of key genes and signaling pathways between flies and humans. Moreover, Drosophila has a lower genetic redundancy in comparison to mammals. These factors, in addition to the advancement of genetic toolkits for manipulating gene expression, allow for the generation of complex Drosophila genotypes and phenotypes. Numerous studies have successfully created Drosophila models for colorectal, lung, thyroid, and brain cancers. These models were utilized in the high-throughput screening of FDA-approved drugs which led to the identification of several compounds capable of reducing proliferation and rescuing phenotypes. More noteworthy, Drosophila has also unlocked the potential for personalized therapies. Drosophila ‘avatars’ presenting the same mutations as a patient are used to screen multiple therapeutic agents targeting multiple pathways to find the most appropriate combination of drugs. The outcomes of these studies have translated to significant responses in patients with adenoid cystic carcinoma and metastatic colorectal cancers. Despite not being widely utilized, the concept of in vivo screening of drugs in Drosophila is making significant contributions to the current drug discovery pipeline. In this review, we discuss the application of Drosophila as a platform in anticancer drug discovery; with special focus on the cancer models that have been generated, drug libraries that have been screened and the status of personalized therapies. In addition, we elaborate on the biological and technical limitations of this system.https://www.frontiersin.org/articles/10.3389/fgene.2022.949241/fullDrosophila melanogastercancer modelshigh-throughput screeningdrug discoverypersonalized therapy |
| spellingShingle | Chamoné Munnik Malungi P. Xaba Sibusiso T. Malindisa Bonnie L. Russell Bonnie L. Russell Selisha A. Sooklal Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies Frontiers in Genetics Drosophila melanogaster cancer models high-throughput screening drug discovery personalized therapy |
| title | Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies |
| title_full | Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies |
| title_fullStr | Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies |
| title_full_unstemmed | Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies |
| title_short | Drosophila melanogaster: A platform for anticancer drug discovery and personalized therapies |
| title_sort | drosophila melanogaster a platform for anticancer drug discovery and personalized therapies |
| topic | Drosophila melanogaster cancer models high-throughput screening drug discovery personalized therapy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.949241/full |
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