Can Any Drug Be Repurposed for Cancer Treatment? A Systematic Assessment of the Scientific Literature

SIMPLE SUMMARY: Drug repurposing strategies utilize drugs, already approved by regulatory authorities, to test their efficacy against different diseases. While this approach is increasingly used, according to the literature, there are few systematic assessments of these efforts so far. In this work, we tried to answer the question: How many approved drugs show anti-cancer effects according to the literature? We found that the majority (69%) of the approved drugs we analyzed did show anti-cancer effects in preclinical studies. The assessment of the methodological quality of the reports, namely, the reporting quality and usage of bias-reducing methods, showed that the methodological quality of the articles was by and large moderate, while many items of the quality assessment were lacking in most reports (for example, blinding, preregistration, power calculations, and detailed information on lab animals). We hypothesize that the current reward systems favor positive results over high methodological quality, probably leading to many false-positive results. ABSTRACT: Drug repurposing is a complementary pathway for introducing new drugs against cancer. Broad systematic assessments of ongoing repurposing efforts in oncology are lacking, but may be helpful to critically appraise current and future efforts. Hence, we conducted a systematic PubMed search encompassing 100 frequently prescribed and 100 randomly selected drugs, and assessed the published preclinical anti-cancer effects. Furthermore, we evaluated all the identified original articles for methodological quality. We found reports indicating anti-cancer effects for 138/200 drugs, especially among frequently prescribed drugs (81/100). Most were reports suggesting single-agent activity of the drugs (61%). Basic information, such as the cell line used or control treatments utilized, were reported consistently, while more detailed information (e.g., excluded data) was mostly missing. The majority (56%) of in vivo studies reported randomizing animals, while only few articles stated that the experiments were conducted in a blinded fashion. In conclusion, we found promising reports of anti-cancer effects for the majority of the assessed drugs, but speculate that many of them are false-positive findings. Reward systems should be adjusted to encourage the widespread usage of high reporting quality and bias-reducing methodologies, aiming to decrease the rate of false-positive results, and thereby increasing the trust in the findings.