Multiple Myeloma: Possible Cure from the Sea

Abstract

Multiple myeloma (MM) is a blood cancer that occurs in the plasma cells (PCs), a type of white blood cell. Despite the progress of several current treatments that prolong the overall patient’s survival, most MM cases are incurable. For this reason, many efforts have been undertaken by the scientific community in the search for new treatments. BLENREPTM and Aplidin® are two marine-derived drugs currently in use for MM. In addition, other natural products have been identified from marine organisms, tested for their possible anticancer properties, and are in preclinical or clinical trials for MM, including cytarabine, a compound in use for leukaemia treatment. Between the most successful marine compounds in fighting MM, there are molecules with specific targets, such as the elongation factor 1-alpha 2 and proteasome inhibitors, and compounds conjugated with antibodies that recognise specific cell types and direct the drug to the correct cell target. Active compounds belong to different chemical classes, from cyclic peptides to alkaloids, highlighting the importance of screening the plethora of compounds produced by marine organisms. In this review, we summarise the current state of art of MM therapies focusing on the marine natural product emerging roles.

Natural Agents as Novel Potential Source of Proteasome Inhibitors with Anti-Tumor Activity: Focus on Multiple Myeloma

“…This is even more the case for anticancer drugs, for which the 25% of the approved compounds are of natural origin or Nature-derived [ 45 ]. Given the relevance of the proteasome as therapeutic target in MM, the search for natural PIs has significantly intensified in the last several decades [ 21 ].…”

“…Importantly, marine-derived natural compounds isolated from sponges, mollusks, cyanobacteria, corals and tunicates have been clinically approved for MM by the US and Australian FDA as well as the European Medicines Agency (EMA), such as belantamab mafodotin and plitidepsin, while others are under clinical trial or extensive preclinical assessment [ 21 ].…”

Recent Advancement in Anticancer Compounds from Marine Organisms: Approval, Use and Bioinformatic Approaches to Predict New Targets

“…Another member of this family is the didemnin B, previously found in the Caribbean Trididemnum solidum , but due to its neuromuscular toxicity, studies were stopped, preferring the well-tolerated and more active plitidepsin. The difficulty to harvest and cultivate the organisms slowed down the studies, even if the anti-tumor activity was really interesting [ 55 , 56 ]. Nowadays, thanks to a deeper knowledge of aquaculture systems and cultivation methods and a fine use of the multi-step total synthesis processes, it is easy to produce this depsipeptide, preserving the marine ecosystem.…”

Nortopsentins as Leads from Marine Organisms for Anticancer and Anti-Inflammatory Agent Development

“…The first marine-derived drug on the market was Cytosar ® , whose active compound acting as an inhibitor of DNA polymerase, cytarabine (Ara-C), is a synthetic analogue of a C-nucleoside isolated from the Caribbean sponge Tethya crypta . Cytosar ® was approved by the Food and Drug Administration (FDA) in 1969 for the treatment of leukaemia and lymphoma ( Table 1 ) [ 17 , 18 , 21 ]. Another drug available on the market is Halaven ® , which was accepted by the FDA in late 2010 as a chemotherapy agent for the treatment of metastatic breast cancer.…”