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Title: Repurpose anti-diabetic drugs for cancer based on causal evidence Authors:  Shenbo Xu - Massachusetts Institute of Technology (United States) [presenting]
Stan Finkelstein - MIT (United States)
Roy Welsch - Massachusetts Institute of Technology (United States)
Bowen Su - Imperial College London (United Kingdom)
Bang Zheng - Imperial College London (United Kingdom)
Marie-Laure Charpignon - MIT (United States)
Ioanna Tzoulaki - Imperial College London (United Kingdom)
Abstract: Cancer has been a worldwide health issue with increasing burden but current effective therapies for most cancer types are limited. This unmet need remains high even though tremendous investments have been made in drug R\&D. As such, drug repurposing, retargeting labelled drugs for off-label diseases, has aroused more and more attention. There are 294,701 type II diabetic patients with at least one anti-diabetes prescription within Clinical Practice Research Datalink (CPRD). Among these participants, 148,983 (50.6\%) individuals started by metformin monotherapy and 61,741 (21.0\%) initiated sulfonylureas monotherapy. Due to analogous pretreatment clinical indications and the number of anti-diabetic drug users, we limit our cohort to metformin and sulfonylureas monotherapy initiators. Leveraging enriched EHR data with diagnosis, therapy, lab test and demographic information, we intend to repurpose anti-diabetic drugs for cancer incidence and mortality risks by emulating in-silico clinical trials among aging population based on causal evidence. In general, metformin revealed a statistically significant protective effect over sulfonylureas on cancer mortality risk, whereas their risk on cancer incidence is similar. Moreover, we have offered a systematic approach to repurpose other drugs for other diseases of interest, which demonstrate a compelling opportunity and enormous cost-saving on future cancer therapy.