Markus Sjöblom

Chemotherapy-induced intestinal toxicity

Chemotherapeutic drugs induce toxic effects in cancer cells by targeting key cellular mechanisms of rapidly dividing cells, but the drugs are not specific to cancer cells and consequently lead to off-target side effects. One cell type that is particularly sensitive to chemotherapy is the fast-proliferative stem cells in the intestinal epithelium.

Up to 90% of all cancer patients dosed with chemotherapeutic agents experience gastrointestinal (GI) toxicity leading to intestinal mucositis. This inflammation of the mucous membranes lining the GI-tract is manifested by severe diarrhea, increased mucosal permeability and ulcerations but also pain, infections and weight loss, thus contributing to a decreased quality-of-life. These side-effects often necessitate a dose-reduction, thus limiting therapeutic efficiency and can in itself also form a life-threatening condition in weak and vulnerable patients.

The interest of my lab is in studying mechanisms which hold the potential to reduce intestinal chemotherapy-induced mucositis and to develop new intervention strategies that improve the treatment of cancer.

At the moment we are working on elucidating the effects melatonin, free radical scavengers, and anti-inflammatory drugs for chemotherapy-induced intestinal mucositis in vivo. Our preferred model system is the rat, but also mice. In collaboration, we investigate mechanisms using intestinal organoids.

Physiological parameters that we are studying is mucosal permeability, ion secretion, fluid absorption/secretion and intestinal motility in combination with histology and different molecular techniques.

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