Drug repurposing has emerged as a pivotal strategy in pharmaceutical research, presenting a pathway to accelerate clinical translation and significantly reduce the costs associated with traditional drug discovery methods. However, researchers require information into the underlying causes of the disease and drug responses to successfully repurpose a drug. This is where transcriptomics – the study of RNA molecules on a cell or population of cells — comes to the fore i.
Finding new applications for drugs
At its essence, drug repurposing entails the exploration of new therapeutic applications for existing drugs, capitalizing on their well-established safety profiles and pharmacological properties. This innovative approach addresses the prolonged timelines, high costs, and elevated failure rates inherent in traditional drug development pipelines, leveraging existing knowledge to streamline the drug development process and provide potential solutions for unmet medical needs ii.
Within pharmaceutical research, drug repurposing shines as a beacon of innovation, complementing traditional drug discovery processes and effectively accelerating the transition from laboratory discovery to clinical application, meeting the pressing demands of patients. Not only does drug repurposing expedite treatment delivery, but it also substantially reduces the costs associated with drug development, thereby promoting efficiency and resource optimization within the pharmaceutical industry iii.
One technique researchers are deploying in drug repurposing is transcriptomics, which enables the analysis of gene expression patterns associated with various diseases and treatments, facilitating the identification of potential therapeutic targets and elucidation of drug modes of action in the context of repurposing existing drugs.
Additionally, transcriptomics aids in the discovery of biomarkers essential for patient stratification, enhancing the efficiency of drug repurposing efforts and accelerating the development of innovative treatments with potential applications across multiple disease indications.
Through comprehensive analysis of gene expression dynamics, transcriptomics not only streamlines the drug repurposing process but also enables a deeper understanding of disease pathogenesis and drug interactions, ultimately paving the way for more effective and personalized therapeutic interventions iv.
One notable example of successful drug repurposing facilitated by transcriptomics is the use of thalidomide for the treatment of multiple myeloma v. Originally developed as a sedative and antiemetic agent, thalidomide was withdrawn from the market in the 1960s due to its teratogenic effects. However, transcriptomic studies revealed that thalidomide possesses immunomodulatory properties and inhibits angiogenesis, suggesting its potential utility in cancer therapy. Subsequent clinical trials demonstrated the efficacy of thalidomide in combination with other agents for the treatment of multiple myeloma, leading to its approval as a second-line therapy for this indication vi.
Transcriptomic analysis has also played a crucial role in repurposing metformin, a medication primarily used to treat type 2 diabetes, for cancer therapy vii. By scrutinizing metformin’s molecular effects, such as inhibiting mitochondrial complex I, the first enzyme in the respiratory chain, and activating AMPK signaling pathways, transcriptomics has revealed its potential as an anticancer agent. Moreover, transcriptomic studies have identified specific cancer subtypes that exhibit heightened sensitivity to metformin, enabling targeted therapeutic approaches. Clinical trials across various cancer types, including breast, colorectal, and prostate cancer, have shown promising results, affirming the effectiveness of metformin in inhibiting tumor growth and enhancing patient outcomes. This successful repurposing of metformin highlights the transformative power of transcriptomics in identifying new therapeutic applications for existing drugs, ultimately benefiting patients with cancer.
A powerful tool for drug repurposing
As these examples show, transcriptomics is a powerful tool that holds immense promise in the field of drug repurposing, offering a systematic approach to identify new therapeutic opportunities for existing drugs. The successful repurposing of drugs like metformin for cancer treatment highlights the transformative power of transcriptomics in identifying new therapeutic applications for existing drugs, ultimately benefiting patients worldwide.
As transcriptomic technologies continue to advance, their integration into drug repurposing workflows promises to accelerate the development of innovative treatments and address unmet medical needs more effectively. Thus, transcriptomics emerges not only as a tool for understanding disease biology but also as a catalyst for innovation in drug discovery and development.
About the author:
Antonio Gomez is Associate Director in Data Science at PharmaLex. He has more than 15 years of experience in OMICs technologies for target discovery and biomarker development.
Notes:
i Transcriptomics. DOI: 10.1016/B978-0-12-821618-7.00157-7. https://www.sciencedirect.com/science/article/abs/pii/B9780128216187001577
ii Drug repurposing: progress, challenges and recommendations. DOI: 10.1038/nrd.2018.168 https://www.nature.com/articles/nrd.2018.168
iii Drug repurposing: a nexus of innovation, science, and potential. DOI: 10.1038/s41598-023-44264-7 https://www.nature.com/articles/s41598-023-44264-7
iv Drug Repurposing From Transcriptome Data: Methods and Applications. DOI: 10.1016/ B978-0-12-816125-8.00011-0 https://www.sciencedirect.com/science/article/abs/pii/B9780128161258000110
v Utilization of translational bioinformatics to identify novel biomarkers of bortezomib resistance in multiple myeloma. DOI: 10.7150/jca.9864. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216795/
vi A drug repositioning success: The repositioned therapeutic applications and mechanisms of action of thalidomide” DOI: 10.1177/1078155220975825. https://pubmed.ncbi.nlm.nih.gov/33249990/7vi Metformin: A promising drug for human cancers ” DOI: 10.3892/ol.2022.13325. https://pubmed.ncbi.nlm.nih.gov/35720480/
vii Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin” DOI: 10.1038/s41416-019-0665-5. https://pubmed.ncbi.nlm.nih.gov/31819193/
