Effect of ageing on a chemically induced colon cancer model

Colorectal cancer is one of the most common cancers in the world and in Austria, where it makes up 23 % of all newly diagnosed cancers in men and 10 % in women. Colorectal cancer is one of the most lethal forms of cancer. More than one-third of all patients who are diagnosed with colorectal cancer in Austria die within 5 years. The foremost risk factor for developing this cancer is age: on average, patients who are diagnosed with sporadic colorectal cancer are about 70 years old and the likelihood for developing this cancer keeps rising with advancing age. Following age, the next major risk factor for the development of colorectal cancer is chronic inflammation of the colon (inflammatory bowel disease) and the risk for colitis-associated colorectal cancer rises with advancing age. Very little is known about the influence of ageing on treatment or preventative measures against sporadic colorectal cancer. Older persons are vastly underrepresented in trials for new cancer medicines, even though the metabolism of anti-cancer drugs and the reaction of the body to the drugs changes with advancing age. This is also true for preclinical experiments (animal studies), which are routinely used to test new anti-cancer medications before they can be tested on humans. Indeed, almost all animal studies, which focus on developing treatments against sporadic or colitis-associated colorectal cancer, are performed exclusively on very young mice (ranging from 5-12 weeks, which roughly corresponds to 10-25 year old humans), even though they are supposed to model a disease that predominately affects elderly patients. That means that drugs, which are being developed for a disease that affects mostly older patients, are predominantly tested in animals representing children or young adults. This is very problematic because it reduces the relevance and thus the applicability of the model for selecting candidate drugs for clinical trials. Moreover, it affects also animal welfare, as less adequate models means that more animals need to be used for trials. In our project, we will address this problem by testing whether there is difference in the outcome of drug-testing experiments depending on the age of the animals. We will investigate both the impact of animal age on a standard preventive medicinal treatment as well as a nutritional healthy cancer-preventative diet against the development of colitis associated colorectal cancer. Using this systematic study, we will be able to determine whether older mice indeed do react differently to pharmacological or nutritional interventions against colorectal cancer development. This will allow us to either validate or change the current practice of using young mice as a model for aged patients.