LXR Activation Promotes Intestinal Healing and Suppresses Colorectal Cancer Growth

Key Insights

• Researchers at Karolinska Institutet discovered that activating the Liver X receptor (LXR) promotes intestinal regeneration after damage.
• The study found LXR activation can simultaneously suppress tumor growth in colorectal cancer, offering a dual therapeutic effect.
• The findings suggest LXR activation could lead to new treatments for inflammatory bowel disease (IBD) and prevent bowel disorders post-cancer therapy.

Researchers at Karolinska Institutet have identified a molecule that aids intestinal healing and inhibits colorectal cancer tumor growth. Published in Nature, the study reveals that activating the Liver X receptor (LXR) promotes tissue regeneration and suppresses tumor development, potentially leading to new treatments for inflammatory bowel disease (IBD) and mitigating chronic bowel disorders following cancer treatments.

Dual Function of LXR

The research team, led by Srustidhar Das and Eduardo J. Villablanca, focused on identifying novel therapeutic strategies for IBD, as many patients do not respond to current treatments. They discovered that LXR activation could promote mucosal healing through tissue regeneration—a beneficial alternative to immunosuppressive drugs. "We've now identified a molecule that can help the intestines to heal after damage while suppressing tumour growth in colorectal cancer," says Srustidhar Das.

Study Details and Methodology

The researchers employed advanced technologies, including transcriptome mapping of intestinal cells, 3D organoids, and spatial transcriptomics. These methods allowed them to observe and validate the dual functionality of LXR. The spatial transcriptomics, developed at SciLifeLab by scientists from the Royal Institute of Technology (KTH) and Karolinska Institutet, enabled detailed mapping of gene expression in different tissues.

Clinical Implications

Each year, over 7,000 people in Sweden are diagnosed with bowel or rectal cancer, often undergoing chemotherapy and radiotherapy, which can cause chronic intestinal inflammation. Eduardo J. Villablanca notes, "This new therapeutic molecule has the potential to treat not only IBD patients but also cancer patients to prevent chronic bowel disorders after radiotherapy and/or chemotherapy."

The study's findings suggest that LXR activation could address the unmet need for effective IBD treatments and reduce the risk of bowel complications in cancer patients. Further research is needed to fully understand how LXR controls tumor formation.