Advancing Treatment Approaches for Coeliac Disease-Associated Lymphoma – RefracTher

Coeliac disease (CeD), or gluten intolerance, is one of the most common digestive disorders. A rare complication of CeD is the development of enteropathy-associated lymphomas (EATL), often preceded by a low-grade clonal intraepithelial lymphoproliferation known as refractory CeD type 2 (RCD2).
Recently, our laboratory has demonstrated that gain-of-function mutations in JAK1 and/or STAT3 are found in most lymphomas complicating CeD. These findings pave the way for a therapeutic approach targeting the JAK1-STAT3 pathway, especially at the early stages of low-grade lymphocyte proliferation, when these cells are resistant to chemotherapy. However, concerns remain regarding the potential adverse effects of therapies targeting the JAK1-STAT3 pathway, which may promote the emergence of resistant tumor subpopulations, necessitating the development of alternative therapeutic approaches.
To address this question, we will rely on our preliminary results and access to a cohort of RCD2 patients to pursue three complementary objectives: the analysis of intra-tumor heterogeneity, the assessment of the risk associated with targeted therapy using JAK1 inhibitors, and the identification of alternative therapeutic options. These objectives aim to better understand the disease progression and develop effective therapeutic approaches for patients with RCD2.