A systematic review of key molecules prognostic and diagnostic models and therapeutic strategies in cuproptosis of multiple myeloma

Cuproptosis, a novel form of programmed cell death, is closely implicated in the pathogenesis and progression of multiple myeloma (MM), a common hematological malignancy with limited therapeutic efficacy for relapsed/refractory cases. Its core biological features involve copper homeostasis imbalance-induced abnormal accumulation of lipoylated proteins and loss of iron-sulfur cluster proteins. Key regulatory molecules modulate MM cell proliferation, apoptosis, and drug resistance through interactions with metabolic pathways and the tumor immune microenvironment. Clinically, cuproptosis-related genes (CRGs) and long non-coding RNAs (lncRNAs) have potential clinical value in preclinical studies as prognostic biomarkers with potential auxiliary diagnostic reference value, with constructed models demonstrating superior risk stratification efficacy over traditional staging systems. Therapeutically, cuproptosis inducers and targeted agents against key regulators exhibit potential in reversing MM drug resistance, especially when combined with proteasome inhibitors (PI) or immunotherapies. In this review, we systematically summarize the molecular mechanisms and biological functions of cuproptosis, and elucidate the potential therapeutic value and underlying mechanisms of cuproptosis in multiple myeloma based on published preclinical experiments and clinical trial data. Rigorous investigation of this field will provide novel insights into personalized prognostic stratification and therapeutic implications, ultimately improving clinical outcomes in patients with MM.