Marine-Derived Anticancer Agents: Clinical Benefits, Innovative Mechanisms, and New Targets

Abstract

The role of the marine environment in the development of anticancer drugs has been widely reviewed, particularly in recent years. However, the innovation in terms of clinical benefits has not been duly emphasized, although there are important breakthroughs associated with the use of marine-derived anticancer agents that have altered the current paradigm in chemotherapy. In addition, the discovery and development of marine drugs has been extremely rewarding with significant scientific gains, such as the discovery of new anticancer mechanisms of action as well as novel molecular targets. Approximately 50 years since the approval of cytarabine, the marine-derived anticancer pharmaceutical pipeline includes four approved drugs and eighteen agents in clinical trials, six of which are in late development. Thus, the dynamic pharmaceutical pipeline consisting of approved and developmental marine-derived anticancer agents offers new hopes and new tools in the treatment of patients afflicted with previously intractable types of cancer.

Marine Cyanobacteria and Microalgae Metabolites—A Rich Source of Potential Anticancer Drugs

“…Salinosporamide A did not induce peripheral neuropathy, thrombocytopenia, or myelosuppression, which were observed with other proteasome inhibitors [83]. Similarly, Phase II findings showed enhanced therapeutic function and increased duration of the inhibition of the proteasome [75]. Both the United States Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) declared it to be an orphan medicine targeting multiple myeloma [75].…”

“…Even so, it was the basis for more efficient derivatives to come into existence. One of its derivatives, the monoclonal antibody-drug conjugate Brentuximab vedotin (Adcetris) has been licensed for its anticancer activity against Hodgkin's lymphoma [75].…”

“…Similarly, Phase II findings showed enhanced therapeutic function and increased duration of the inhibition of the proteasome [75]. Both the United States Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) declared it to be an orphan medicine targeting multiple myeloma [75]. At present salinosporamide is undergoing Phase III studies for newly diagnosed cases of glioblastoma [75].…”

“…Interestingly, even though it reached Phase II of the clinical trials, its development has been halted due to severe side effects [141]. Lagunamide A (75) and B (76) (Figure 11) are cyclic depsipeptides extracted from the marine cyanobacterium Lyngbya majuscule. Both the metabolites exhibited potent cytotoxicity against P388 (a murine leukemia cell line) [142].…”

Metabolites from marine invertebrates and their symbiotic microorganisms: molecular diversity discovery, mining, and application

“…To date, there have been 13 approved therapeutic agents that could be considered derivatives of MNPs (Altmann 2017;Jiménez 2018;Newman 2019;Pereira et al 2019). Moreover, more than 30 MNP derivatives constitute the global marine pharmaceutical clinical pipeline in Phases III, II or I of drug development (According to the following websites: http:// marin ephar macol ogy.midwe stern .edu; http://pharm a.id.infor ma.com (accessed on August 6, 2019); Jiménez 2018; Newman 2019; Pereira et al 2019). The significant potential for new drug development based on MNPs in all disease areas has been previously discussed (Newman and Cragg 2016a).…”