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Breaking through Multiple Myeloma: A Paradigm for a Comprehensive Tumor Ecosystem Targeting

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BIOMEDICINES
卷 11, 期 7, 页码 -

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MDPI
DOI: 10.3390/biomedicines11072087

关键词

multiple myeloma; microenvironment; immunotherapy; monoclonal antibody

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Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells in the bone marrow, leading to multiple bone lesions. Over the past two decades, significant advancements have been made in the development of novel therapeutics for MM, improving patient outcomes and overall survival. These advancements include thalidomide and its derivatives, proteasome inhibitors, monoclonal antibodies, and CAR-T-based strategies, which target neoplastic plasma cells and the tumor microenvironment.
Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival. These advancements include thalidomide and its derivatives, lenalidomide and pomalidomide, which exhibit diverse mechanisms of action against the plasma cell clone. Additionally, proteasome inhibitors such as bortezomib, ixazomib, and carfilzomib disrupt protein degradation, proving specifically toxic to cancerous plasma cells. Recent advancements also involve monoclonal antibodies targeting surface antigens, such as elotuzumab (anti-CS1) and daratumumab (anti-CD38), bispecific t-cell engagers such as teclistamab (anti-BCMA/CD3) and Chimeric antigen receptor T (CAR-T)-based strategies, with a growing focus on drugs that exhibit increasingly targeted action against neoplastic plasma cells and relevant effects on the tumor microenvironment.

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