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

ORCID
0000-0002-2293-9698
Affiliation
Unit of Internal Medicine and Clinical Oncology “G. Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro Medical School, 70124 Bari, Italy;
Solimando, Antonio G.;
ORCID
0000-0003-0917-4173
Affiliation
Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, 97080 Würzburg, Germany;
Krebs, Markus;
ORCID
0000-0003-1942-2601
Affiliation
Department of Precision and Regenerative Medicine and Ionian Area, Pharmacology Section, University of Bari Aldo Moro Medical School, 70124 Bari, Italy;(V.D.);(I.C.C.)
Desantis, Vanessa;
Affiliation
Unit of Internal Medicine and Clinical Oncology “G. Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro Medical School, 70124 Bari, Italy;
Marziliano, Donatello;
Affiliation
Department of Precision and Regenerative Medicine and Ionian Area, Pharmacology Section, University of Bari Aldo Moro Medical School, 70124 Bari, Italy;(V.D.);(I.C.C.)
Caradonna, Ingrid Catalina;
Affiliation
Orthopedics and Traumatology Unit ASL BA-Ospedale della Murgia “Fabio Perinei”, 70022 Altamura, Italy
Morizio, Arcangelo;
Affiliation
IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
Argentiero, Antonella;
ORCID
0000-0002-4909-0436
Affiliation
Gastroenterology Unit, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy
Shahini, Endrit;
ORCID
0000-0002-1154-0964
Affiliation
Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany
Bittrich, Max

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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