Sander zooming in on the awarded grant

Research: “Identification and validation of targets to treat gut barrier dysfunction in human cancer cachexia”

Duration of research: five years

Grant: 750,000 euros

Sander Rensen leads the project; co-applicants are Kaatje Lenaerts and Frank Schaap from the Department of Surgery at Maastricht University/NUTRIM, and Klaske van Norren from Wageningen University & Research. Other project team members include Steven Olde Damink and Tim Lubbers (Surgery MUMC+), and Dana Mustafa from Erasmus MC and Natal van Riel from Eindhoven University of Technology. In line with the specific goals of the ZonMw Open programme, this project team combines unique synergistic expertises in the spirit of team science.

Sander Rensen zooming in on this grant and the research

This is a translational study (with patients but also with tissues and cell models of these patients) into the causes of weight loss in people with cancer. Despite knowing that weight loss leads to shorter survival and poor quality of life in patients, we do not yet know why this weight loss occurs. For this study, we zoom in on the role of inflammation and how bacterial substances that can 'leak' from the gut to the rest of the body contribute to this.

Cachexia is the medical term for weight loss that cannot be prevented by dietary interventions. Cachexia is common in patients with cancer and makes treatments less successful. In one in five patients with cancer, cachexia is the direct cause of death. It is unclear how cachexia develops and therefore, there is no treatment for it. However, it is known that inflammation (the body's response to pathogens and injury) plays a central role. We will investigate whether the intestines of patients with cachexia are less effective in preventing the entry of bacterial agents that cause inflammation in the body. We will measure intestinal barrier function in patients with and without cachexia, and study possible causes of disturbed intestinal integrity. Using this knowledge, we will identify and test treatments aiming to improve the barrier. The ultimate goal of our work is to prevent weight loss, and thereby improve both treatment outcomes and quality of life of patients with cancer.

About the research study

We are going to study the function of the intestinal barrier from 100 people with colon cancer or pancreatic cancer (who have varying degrees of weight loss). When these people undergo surgery to remove the tumour, we will take a piece (biopsy) of the bowel. This will be used to analyse the different cells that determine the barrier function of the intestine using a novel spatial transcriptomics approach. We also make so-called organoids of their tissues, both from the tumour (generating mini-tumours that we can grow and study in the lab) and from intestinal cells. With these, we will study the influence of substances made by the patients' tumour cells on the function of their intestinal cells.

What impact do you hope to make?

We expect that this will allow us to identify the molecular causes of impaired gut barrier function in people with cancer-induced weight loss, and eventually identify new targets for weight loss treatment.

We hope this will allow us to find effective ways to combat weight loss in people with cancer, so that both their survival and quality of life will improve.

More on the ZonMW Open Competitie grant:

https://www.zonmw.nl/nl/nieuws/subsidie-voor-29-vernieuwende-onderzoeksteams-vanuit-zonmw-open-competitie.

Dr Sander Rensen is molecular cell biologist by training and applies this background in translational research studies. His research group focuses on the disturbances of metabolism in cancer cachexia.