The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review

Multiple myeloma (MM) is a B-cell malignancy involving monoclonal plasma cells that produce nonfunctional immunoglobulins. It is still incurable due to de novo or acquired resistance of malignant cells to standard chemotherapies. Thus, understanding the mechanism of therapeutic resistance is essential to develop better interventions and identifying new therapeutic targets. MM is a heterogeneous disease characterized by complex genetic alterations, which are critical for prognostic stratification. Due to the heterogeneity and clinical challenges associated with MM, there remains a critical need for novel biomarkers to improve both early diagnosis and prognostic accuracy. Antioxidants participate in protecting cancer cells from the damaging effects of oxidative stress by neutralizing reactive oxygen species. These molecules may have their own role in myeloma progression and drug resistance. However, studies reported contradictory ideas regarding the levels and roles of antioxidants in MM. The main aim of this review is to conceptualize the diagnostic, prognostic, and therapeutic significance of common antioxidants for MM. The most common antioxidant systems discussed in this study were DJ-1, glutathione, thioredoxin, and superoxide dismutase. The review revealed that antioxidants are overexpressed in myeloma cells compared to normal plasma cells. This excess expression of antioxidants increases tumor cells' survival and their chemoresistance leads to poor prognosis and short survival of myeloma patients. Thus, antioxidants and their synthesis pathways may have a promising prognostic, diagnostic, and therapeutic role in MM. Vitamin C (ascorbic acid), on the other hand, has a two-faced role in cancer, including MM. It can function as an antioxidant (increase myeloma cell resistance to chemotherapy) or pro-oxidant (enhance the therapeutic effect of myeloma drugs), depending on its dose and route of administration. Pharmacological (ultra-high) doses of vitamin C administered intravenously may act as a pro-oxidant that can selectively kill myeloma cells by elevating the cellular labile iron pool and generating extracellular H₂O₂.