Mechanisms of chemoresistance in diffuse large B‑cell lymphoma and novel therapeutic strategies (Review).

Diffuse large B‑cell lymphoma (DLBCL), the most prevalent subtype of lymphoma, is characterized by rapid growth and a poor prognosis, with the R‑CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) being the standard first‑line therapy. However, 30‑40% of patients experience early relapse or refractoriness to treatment, highlighting the need to understand the mechanisms of chemoresistance. The present review synthesizes the current knowledge on the molecular mechanisms underlying chemoresistance in DLBCL, including genetic mutations, epigenetic modifications, aberrant activation of signaling pathways, alterations in drug metabolism and efflux, and upregulation of anti‑apoptotic proteins. In addition, the role of the tumor microenvironment in mediating therapeutic resistance is discussed and biomarkers associated with chemoresistance are explored. Furthermore, novel therapeutic strategies targeting chemoresistance, such as immunotherapy, metabolic modulators and epigenetic therapies, are examined. Understanding these mechanisms is crucial for developing effective treatment strategies to overcome resistance and improve patient outcomes in DLBCL.