Title: Repurposing approved drugs to target metabolic flexibility in ovarian cancer cells in the tumour microenvironment
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Over the past 40-years, UK ovarian cancer incidence-rates have increased by 14% and are projected to rise by another 15% by 2035 (Cancer Research UK). Of all UK countries, Wales has one of the highest incidence-rates and one of the highest rates of death. Unfortunately, more than three-quarters of patients present with a late-stage aggressive disease that is highly likely to become chemotherapy-resistant, often leaving surgery or end-of-life care as the only options. Treatments are limited and, on the whole, have not changed in more than 40-years. However, developing brand-new drugs is an incredibly expensive (around $3 billion) and arduous-process, taking around 9-years to reach clinical trials and 15-years to market; and has a success-rate of only around 5% in cancer. Indeed, despite increased spending on research, the number of new drug discoveries has actually decreased since the 1990s. Thus, there is an urgent need for an alternate and complimentary approach to treating chronic therapy-resistant ovarian cancer. Drug repurposing is the process of finding new uses for existing drugs, outside the scope of their original disease target. Repurposing drugs has several important advantages: risks are reduced, as repurposing drug candidates have already been through several stages of clinical-development and safety-checks in humans; timeframes from initial research to clinical trials can be halved; and the costs of getting the repurposed drugs to market can be 100s of times lower than for brand-new drugs. In this study, we propose to use drug combinations that have shown anticancer properties in addition to their original disease target, such as metformin (type-2 diabetes), syrosingopine (high-blood pressure) and diclofenac (rheumatoid arthritis). Encouragingly, combinations of these drugs have been shown to eradicate tumours in cancer models. Here, with pilot data, we show that this strategy holds great promise in the treatment of chronic and debilitating ovarian cancer.

Lay abstract: Over the past 40-years, UK ovarian cancer incidence-rates have increased by 14% and are projected to rise by another 15% by 2035 (Cancer Research UK). Of all UK countries, Wales has one of the highest incidence-rates and one of the highest rates of death. Unfortunately, more than three-quarters of patients present with a late-stage aggressive disease that is highly likely to become chemotherapy-resistant, often leaving surgery or end-of-life care as the only options. Treatments are limited and, on the whole, have not changed in more than 40-years. However, developing brand-new drugs is an incredibly expensive (around $3 billion) and arduous-process, taking around 9-years to reach clinical trials and 15-years to market; and has a success-rate of only around 5% in cancer. Indeed, despite increased spending on research, the number of new drug discoveries has actually decreased since the 1990s. Thus, there is an urgent need for an alternate and complimentary approach to treating chronic therapy-resistant ovarian cancer. Drug repurposing is the process of finding new uses for existing drugs, outside the scope of their original disease target. Repurposing drugs has several important advantages: risks are reduced, as repurposing drug candidates have already been through several stages of clinical-development and safety-checks in humans; timeframes from initial research to clinical trials can be halved; and the costs of getting the repurposed drugs to market can be 100s of times lower than for brand-new drugs. In this study, we propose to use drug combinations that have shown anticancer properties in addition to their original disease target, such as metformin (type-2 diabetes), syrosingopine (high-blood pressure) and diclofenac (rheumatoid arthritis). Encouragingly, combinations of these drugs have been shown to eradicate tumours in cancer models. Here, with pilot data, we show that this strategy holds great promise in the treatment of chronic and debilitating ovarian cancer.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS