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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Drug repurposing: new options for prevention and treatment of colorectal and breast cancer

Alternative title: Nye muligheter for vanlig brukte legemidler i prevensjon og behandling av tarmkreft og brystkreft

Awarded: NOK 8.0 mill.

Project Number:

301628

Project Period:

2020 - 2023

Location:

Subject Fields:

Partner countries:

The reducing costs of DNA sequencing has paved the way for precision medicine, but in spite of the enormous investments, the development of new cancer drugs has proven difficult. The price of new drugs have also exploded, increasing the burden on health economies worldwide. Being able to utilize existing well-tolerated non-cancer drugs as a part of the cancer treatment and prevention is an attractive and cost-effective strategy that likely also will result in fewer side effects. Both preclinical and epidemiological studies suggest that a number of commonly used drugs may have anti-cancer properties. In this project, the researchers focus on breast cancer and colorectal cancer, which are two of the most common cancers in Norway. The project investigates if use of certain commonly used drugs, namely metformin, beta-blockers and aspirin, can improve the prognosis and reduce the risk of those two cancers. The researchers are particularly interested in exploring new therapeutic options for aggressive cancer subtypes that have limited treatment choices, such as triple negative breast cancer. The researchers study the potential of the three drugs from different angles: first linking data from the Cancer Registry of Norway, the Norwegian Prescription Database and other registries, to investigate how the use of these drugs affect cancer incidence and prognosis in the Norwegian population. The most promising results will then be investigated further in cell experiments, where the drugs will be tested directly on cancer cells. In addition, the researchers will test in mouse models if cancer spreads differently in mice treated with standard-of-care and in mice treated with standard-of-care plus the non-cancer drugs under investigation.

The development of new targeted therapies for cancer has proven difficult, and prices of new drugs have exploded, increasing the burden on health economies. Repurposing the large arsenal of approved non-cancer drugs is an attractive strategy to offer additional preventive and treatment options. We will seek evidence to support new use of nonsteroidal anti-inflammatory drugs (e.g. aspirin), metformin and beta-blockers for colorectal cancer (CRC) and breast cancer (BC) by analysing prescription and cancer record linkage data from approximately 3 million Norwegian residents aged 18-79 years in 2004, followed from 2004 until 2017. We will calculate the risk of CRC and BC among users of a specific drug and compare it to the risk in non-users of the same drug. In individuals with cancer we will evaluate prognosis in users and non-users of a specific drug. Also, we will provide original evidence on possible synergistic effects between drugs. We are particularly interested in exploring new therapeutic options for aggressive cancer subtypes that have limited treatment choices, such as triple negative BC. We will use a multidisciplinary network to explore those associations from different perspectives. With prof Kjetil Taskén at the Institute for Cancer Research, OUH and Center for Molecular Medicine, UiO, we will corroborate our most interesting results through the cancer drug sensitivity screening, a new method for testing a panel of drugs directly on cancer cells. With prof Erica Sloan at the Monash University, Melbourne, Australia, we will test mechanistic hypotheses in mouse models, e.g. if the process of metastatization is different between mice treated with standard-of-care and mice treated with standard-of-care plus non-cancer drugs under investigation. Finally, we will be part of the discussion forum of the randomized clinical trial ASAC, which tests the effect of aspirin in CRC patients, and plan the verification of our main results in that clinical setting.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol