Small intestinal neuroendocrine tumors: an unknown diversity

Small intestine neuroendocrine tumors a rare tumors that have long been perceived and treated as a single disease. However, a team at the Cancer Research Center of Lyon recently revealed that these tumors can be categorized into four distinct groups, opening up new perspectives for the treatment and management of patients diagnosed with these cancers.

Small intestine neuroendocrine tumors are rare tumors that develop from enteroendocrine cells normally involved in the regulation of digestion and hormone production. Although rare, these tumors are actually increasing among the general population, in particular as a result of more accurate diagnosis. While a large proportion of these cancers present a relatively good prognosis, around 10% are much more aggressive. Despite this clinical disparity, small intestine neuroendocrine tumors have until now been considered, and therefore treated, as a single disease.

In a study published in early March in the journal Nature Communications¹ , the CRCL “Gastroenterology and Technologies for Health” team, led by CNRS researcher Benjamin Gibert and Thomas Walter, PU-PH at Hospices Civils de Lyon, has shown that these tumors can in fact be classified into four distinct molecular groups.

Histological image of an intestinal neuroendocrine tumor

Thanks to multi-omics analysis, including genetic, transcriptomic and epigenetic data, the researchers discovered that each of the four groups has distinct characteristics. The first two groups are associated with endocrine cell differentiation patterns, the third with the presence of immune cells, and the last, with the worst prognosis, has so-called mesenchymal properties.

This discovery could lead to improved management of these rare diseases, and the development of appropriate drugs to better counteract the progression of these tumors.

¹Reference: Patte C, Pommier RM, Ferrari A, Fei-Lei Chung F, Ouzounova M, Moullé P, Richaud M, Khoueiry R, Hervieu M, Breusa S, Allio M, Rama N, Gérard L, Hervieu V, Poncet G, Fenouil T, Cahais V, Sertier AS, Boland A, Bacq-Daian D, Ducarouge B, Marie JC, Deleuze JF, Viari A, Scoazec JY, Roche C, Mehlen P, Walter T, Gibert B. Nature Communications. 2025 Mar 4;16(1):2197. doi: 10.1038/s41467-025-57305-8. Comprehensive molecular portrait reveals genetic diversity and distinct molecular subtypes of small intestinal neuroendocrine tumors.