A molecule identified by Karolinska Institutet researchers promotes intestinal healing and suppresses colorectal cancer tumor growth by activating the Liver X receptor, offering potential new treatments for IBD and cancer.
Scientists at Karolinska Institutet have identified a molecule capable of promoting intestinal healing after injury while also inhibiting tumor growth in colorectal cancer. This breakthrough has the potential to pave the way for new therapies targeting inflammatory bowel disease (IBD) and cancer. The findings are detailed in the journal Nature.
Many patients with inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis do not respond to available treatments, highlighting the need to identify novel therapeutic strategies. In a new study published in Nature, researchers propose that promoting mucosal healing through tissue regeneration could be a valid alternative to immunosuppressive drugs.
“However, it’s virtually impossible to promote tissue regeneration without the risk of inducing tumor growth, as cancer cells can hijack the body’s natural healing processes and start to grow uncontrollably,” says lead author Srustidhar Das, research specialist in Eduardo Villablanca’s research group at Karolinska Institutet’s Department of Medicine in Solna. “We’ve now identified a molecule that can help the intestines to heal after damage while suppressing tumor growth in colorectal cancer.”
Liver X Receptor: A Dual Function Molecule
In their search for new ways to treat IBD, the researchers have identified a handful of molecules with drug-candidate potential. They found that activation of a protein called the Liver X receptor (LXR) can promote regeneration and suppress tumor growth in colorectal cancer.
“The discovery of both these functions was astonishing,” says the last author Eduardo J. Villablanca, Docent at Karolinska Institutet. “We now need to study how LXR controls tumor formation more closely.”
The researchers used a collection of advanced technologies to conduct their study, which included mapping the transcriptome of intestinal cells. The researchers also cultivated what are known as 3D organoids: small, three-dimensional cell structures that mimic the function and structure of the body’s own organs, albeit in miniature format. They then used spatial transcriptomics to map the gene expression in the different tissues, a technique that has been developed at SciLifeLab by scientists from the Royal Institute of Technology (KTH) and Karolinska Institutet in Sweden.
Addressing Bowel Cancer and Chronic Inflammation
Every year, over 7,000 people in Sweden develop bowel or rectal cancer, making it the third most common form of cancer in Sweden. Patients are often treated with chemotherapy and radiotherapy, but this can cause irritation and swelling of the bowel mucosa with subsequent chronic intestinal inflammation.
“Thus, 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,” says Eduardo J. Villablanca.
Reference: “Liver X receptor unlinks intestinal regeneration and tumorigenesis” by Srustidhar Das, S. Martina Parigi, Xinxin Luo, Jennifer Fransson, Bianca C. Kern, Ali Okhovat, Oscar E. Diaz, Chiara Sorini, Paulo Czarnewski, Anna T. Webb, Rodrigo A. Morales, Sacha Lebon, Gustavo Monasterio, Francisca Castillo, Kumar P. Tripathi, Ning He, Penelope Pelczar, Nicola Schaltenberg, Marjorie De la Fuente, Francisco López-Köstner, Susanne Nylén, Hjalte List Larsen, Raoul Kuiper, Per Antonson, Marcela A. Hermoso, Samuel Huber, Moshe Biton, Sandra Scharaw, Jan-Åke Gustafsson, Pekka Katajisto and Eduardo J. Villablanca, 20 November 2024, Nature.
DOI: 10.1038/s41586-024-08247-6
The study was conducted with grants from several bodies, including the Swedish Research Council, Formas (The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning), the Silicon Valley Community Foundation, Novo Nordisk, the Swedish Cancer Society, the Knut and Alice Wallenberg Foundation and the Åke Wiberg Foundation.
Two of the authors have reported potential conflicts of interest: Eduardo J. Villablanca has received research funding from the pharmaceutical company F. Hoffmann-La Roche and Srustidhar Das works as a consultant for Cellphi Biotechnology AB.
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