Novel Marine Compounds: Anticancer or Genotoxic?

Expert Opinion on Investigational Drugs, 2003

Oncological diseases for a long time have remained one of the most significant health problems of modern society, which causes great losses in its labour and vital potential. Contemporary oncology still faces unsolved issues as insufficient efficacy of treatment of progressing and metastatic cancer, chemoresistance, and side-effects of the traditional therapy which lead to disabilities among or death of a high number of patients. Development of new anti-tumour preparations with a broad range of pharmaceutical properties and low toxicity is becoming increasingly relevant every year. The objective of the study was to provide a review of the recent data about anti-tumour preparations of marine origin currently being at various phases of clinical trials in order to present the biological value of marine organisms-producers of cytotoxic compounds, and the perspectives of their use in modern biomedical technologies. Unlike the synthetic oncological preparations, natural compounds are safer, have broader range of cytotoxic activity, can inhibit the processes of tumour development and metastasis, and at the same time have effects on several etiopathogenic links of carcinogenesis. Currently, practical oncology uses 12 anti-tumour preparations of marine origin (Fludarabine, Cytarabine, Midostaurin, Nelarabine, Eribulin mesylate, Brentuximab vedotin, Trabectedin, Plitidepsin, Enfortumab vedotin, Polatuzumab vedotin, Belantamab mafodotin, Lurbinectedin), 27 substances are at different stages of clinical trials. Contemporary approaches to the treatment of oncological diseases are based on targeted methods such as immune and genetic therapies, antibody-drug conjugates, nanoparticles of biopolymers, and metals. All those methods employ bioactive compounds of marine origin. Numerous literature data from recent years indicate heightened attention to the marine pharmacology and the high potential of marine organisms for the biomedicinal and pharmaceutic industries.

British Journal of Pharmacology, 2019

Marine natural products have proven, over the last half‐century, to be effective biological modulators. These molecules have revealed new targets for cancer therapy as well as dissimilar modes of action within typical classes of drugs. In this scenario, innovation from marine‐based pharmaceuticals has helped advance cancer chemotherapy in many aspects, as most of these are designated as first‐in‐class drugs. Here, by examining the path from discovery to development of clinically approved drugs of marine origin for cancer treatment—cytarabine (Cytosar‐U®), trabectedin (Yondelis®), eribulin (Halaven®), brentuximab vedotin (Adcetris®), and plitidepsin (Aplidin®)— together with those in late clinical trial phases—lurbinectedin, plinabulin, marizomib, and plocabulin—the present review offers a critical analysis of the contributions given by these new compounds to cancer pharmacotherapy.

Marine Drugs, 2020

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, bel...

The marine environment is a rich source of both biological and chemical diversity. It is very much likely that marine organisms would be wonderful source of biologically active molecules The collection of the marine therapeutics includes molecules with antibiotic, antiviral, antiphrastic, analgesic and anticancer agent from bacteria, cyanobacteria, tunica, fungi, sponge This reviewfocuses on the latest studies and critical research in this field and evidences the immense potential ofmarine organisms as sources of bioactive peptides and other anticancer biomolecules Various anticancer compounds like Aplidine, Bryostatin-1, Didemin B, Dolastation, Ecteinascidine with diverse modes of action, such as, anti-proliferative, antioxidant, anti-microtubule havebeen isolated from marine sources. Traditional chemotherapeutic agents have a range of side effects likefatigue, gastrointestinal distress and depression of immune system which introduces the these sources have been shown to have antioxidantactivity and cytotoxic effect on several human cancers such as leukemia, lymphoma, ovarian, melanoma, breast, bladder, neuroendocrine, prostatic, colon and non-small cell lung cancer very potently.

Clinics, 2018

This review will discuss the contributions of marine natural molecules, a source only recently found to have pharmaceutical prospects, to the development of anticancer drugs. Of the seven clinically utilized compounds with a marine origin, four are used for the treatment of cancer. The development of these drugs has afforded valuable knowledge and crucial insights to meet the most common challenges in this endeavor, such as toxicity and supply. In this context, the development of these compounds will be discussed herein to illustrate, with successful examples provided by cytarabine, trabectedin, eribulin and brentuximab vedotin, the steps involved in this process as well as the scientific advances and technological innovation potential associated with developing a new drug from marine resources.

International Journal of Cancer, 2003

During 2000, marine antitumor pharmacology research aimed at the discovery of novel antitumor agents was published in 85 peer-reviewed articles. The purpose of this article is to present a structured review of the antitumor and cytotoxic properties of 143 marine natural products, many of them novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids and peptides. The organisms yielding these bioactive compounds comprised a taxonomically diverse group of marine invertebrate animals, algae, fungi and bacteria. Antitumor pharmacological studies were conducted with 19 marine natural products in a number of experimental and clinical models that defined or further characterized their mechanisms of action. Potentially promising in vitro cytotoxicity data generated with murine and human tumor cell lines were reported for 124 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anticancer research clearly remains a multinational effort, involving researchers from and the United States. Finally, this 2000 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine antitumor agents continued at the same high level of research activity as during 1998 and 1999.

2000

During 2003 and 2004, marine pharmacology research directed towards the discovery and

European Journal of Cancer, 2004

During 2001 and 2002, marine antitumour pharmacology research aimed at the discovery of novel antitumour agents was published in 175 peer-reviewed articles. The purpose of this paper is to present a structured Review of the antitumour and cytotoxic properties of 97 marine natural products, many of them novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids, and peptides. The organisms yielding these bioactive compounds comprise a taxonomically diverse group of marine invertebrate animals, algae, fungi and bacteria. Antitumour pharmacological studies were conducted with 30 structurally characterised natural marine products in a number of experimental and clinical models which further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human tumour cell lines was reported for 67 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy, is the fact that marine anticancer research was sustained by a collaborative effort, involving researchers from Australia,

Annals of Oncology, 2003