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

Abstract

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.

Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing

“…Repurposed drugs are estimated to take about 6.5 years and cost around USD 300 million to bring to market, compared to 13 to 15 years and USD 2-3 billion for novel drugs. Moreover, repurposed drugs are less likely to fail overall in clinical trials [8,9].…”

“…Drug repurposing encompasses the repositioning of off-patent FDA-approved drugs, failed drugs, and patented drugs for new clinical indications. Generic drugs, off-patent and widely available, are favored for repurposing due to their extensive safety and efficacy data, lower cost, and reduced risk [9]. Patented drugs, protected by patents and typically in latestage trials, have limited accessibility to safety and efficacy data.…”

“…Failed drugs, which did not receive approval due to various reasons, present an opportunity for repurposing, especially for companies aiming to salvage investments. However, accessing safety and efficacy data for failed drugs is challenging, and addressing initial failure issues is crucial for their successful repurposing [9]. One significant advantage in repurposing existing drugs is the wealth of comprehensive data available, including pharmacodynamics, pharmacokinetics, toxicity, and safety profiles in humans.…”

“…Increasingly, computational methods like signature matching screens and genome-wide association studies (GWAS) are favored. For instance, cimetidine, an anti-peptic ulcer drug, has shown promise for lung adenocarcinoma, while anti-psychotic imipramine has exhibited potential for glioblastoma [9]. Artificial intelligence (AI), machine learning (ML), and deep learning aid (DL) in uncovering associations between drugs and diseases through text mining studies [15], such as repurposing aspirin for targeting TP53 and metformin for cancer [9].…”

“…For instance, cimetidine, an anti-peptic ulcer drug, has shown promise for lung adenocarcinoma, while anti-psychotic imipramine has exhibited potential for glioblastoma [9]. Artificial intelligence (AI), machine learning (ML), and deep learning aid (DL) in uncovering associations between drugs and diseases through text mining studies [15], such as repurposing aspirin for targeting TP53 and metformin for cancer [9]. Furthermore, chemical similarity analysis and molecular docking simulations assist in identifying repurposing candidates, exemplified by thalidomide's potential for colon and renal cancer [9].…”