Research Overview

Research investigating cancer treatments has seen many great advances in the previous decades. However, treatments are most effective when cancers are detected at an earlier stage and to date, many cancers are only detected at late stages, where treatment efficacy and survival of patients is reduced.

In the field of cardiovascular medicine, mortality has drastically reduced in the last 30 years. This is linked to a widespread use of risk predictive and preventive strategies: risk factors, for example high blood pressure, can be measured, preventively treated with medication or lifestyle changes, and monitored over time. We strive to bring a similar approach to the clinical management of cancers.

Core Mission

Our core mission is to enable effective risk prediction, screening, and early detection of cancers using a systems biology approach. Cancers are complex diseases involving genetic (inherited) and non-genetic (environmental and lifestyle) factors with a strong individual component: not everyone exposed to risk factors will ultimately go on to develop cancer. We want to identify individuals at risk and help to prevent cancers altogether by targeted and/or general preventive measures.

Due to its complexity and individual component, risk prediction for cancer is more difficult than simply taking a blood pressure measurement. An ideal risk prediction test for cancer needs to integrate genetic factors (inherited risk) as well as lifestyle and environmental factors.

Prof Martin Widschwendter and his research team have been investigating epigenetics and DNA methylation for this purpose. DNA methylation is an extra layer of information superimposed on the DNA, acting as an interface between genetics and the environment. DNA methylation ultimately integrates all factors a cell has been exposed to and leaves a signature on the DNA: this signature can predict cancer, even at remote sites of the body, years before diagnosis. Our current focus hereby lies on women’s cancers. In the FORECEE project, we implemented the use of methylation analysis from routine cervical screening samples for risk prediction for four women’s cancers: breast, ovarian, endometrial, and cervical cancer.

The Epigenome

DNA is the genetic code inside each of our cells, which we inherit from our parents.

The DNA in each of our cells is identical, yet different cells in our body have very distinct functions: skin cells have different functions from those of liver cells, heart muscle cells, or breast tissue cells. Therefore, how can the function and morphology of the cells be different when they all share the same code?

The answer is epigenetics, which is an extra layer of information superimposed on the DNA. Specifically, we look at DNA methylation patterns. Like DNA, we also inherit epigenetic information from our parents, which can be modified throughout life. This happens, for example, during embryonic development, when different cell types of our bodies start to emerge: different cells have different epigenetic signatures (i.e., epigenetic patterns are cell type-specific). While DNA can be considered as the “hardware” of a computer, DNA methylation is comparable to the software that defines which programs are run.

We now know that DNA methylation is not only modified during development but can be changed through a variety of other factors, including ageing, nutrition, exercise, socio-economic status, obesity, smoking, and exposure to hormones and chemicals (even while we are in the womb). Our work has identified signatures associated with environmental exposures.

As DNA methylation integrates genetic information (it is inherited) and non-genetic information (it can be modified by external factors), it is a highly promising candidate for a risk prediction tool, and importantly, cancer cells have distinct methylation patterns which can exist years before diagnosis. We can therefore use the epigenome to monitor the presence of cancer, and recent work suggests that the epigenome may even be able to predict the risk for the future development of cancers. This can be carried out using the “target tissue” of disease itself (e.g., breast tissue for breast cancer), but this is invasive and therefore not feasible for routine population-based screening. Recent work suggests that we may be able to use “surrogate” tissues, such as epithelial cells derived from buccal swabs, to predict individual cancer risk.

In several recent research papers, we have demonstrated the value of these DNA methylation signatures for women’s cancer risk prediction. We are currently working to validate these tools for clinical screening and identify whether we can also use them to monitor risk over time.

Projects

Read more about our ongoing or past projects by clicking on the logos below.

Vision 2040

To make women's cancer a disease of the past by 2040.