Progress in the development and acquisition of anticancer agents from marine sources
M. L. Amador1, J. Jimeno2, L. Paz-Ares3, H. Cortes-Funes3 and M. Hidalgo1
1 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; 2 Pharmamar, SA, Madrid; 3 Hospital Universitario Doce de Octubre, Medical Oncology Department, Madrid, Spain
Key words: aplidine, bryostatin, cancer, dolastatin, ET-743, marine
Since ancient times, nature has been an important source of medicines: a fact illustrated by the large number of natural products currently in use in medical practice. These products have been identified and developed through folklore knowledge of the medicinal properties of plants, animal extracts and minerals. Microorganisms are also a prolific source of novel agents. They have yielded some of the most important pharmaceutical products, such as the antibiotics, penicillin and aminoglycosides, which represent landmarks in the history of medicine.
Almost 60% of drugs approved for cancer treatment are of natural origin. Vincristine, irinotecan, etoposide, taxanes and camptothecines are all examples of plant-derived compounds. Dactinomicine, anthracyclines, mitomycin and bleomycin are anticancer agents derived from microbial sources [1].
Although marine compounds are under-represented in current pharmacopoeia, it is anticipated that the aquatic environment will become an invaluable source of novel compounds in the future. The marine ecosystem represents 95% of the biosphere, and all except one of the 33 animal phyla are represented in aquatic environments [2]. Most sessile marine invertebrates contain a primitive immune system and produce toxic chemicals as a form of defense. Many of these products act as regulators of specific biological functions. Some of them have pharmacological activity due to their specific interactions with receptors and enzymes. Because these substances become immediately diluted by large volumes of seawater, they need to be highly potent on a molar basis, and also have to retain a relatively low solubility [3].
The development of marine compounds as therapeutic agents is still in its infancy due to the lack of an analogous ethno-medical history as compared with terrestrial habitats, together with the relative technical difficulties in collecting marine organisms. Over the last few decades significant efforts have been made, by both pharmaceutical companies and academic institutions, to isolate and identify new marine-derived, natural products. These initiatives have been accompanied by funding support from governmental agencies. Specific programs directed towards the collection and characterization of marine natural products and evaluation of their biological activity have been established [4]. This systematic investigation of marine environments is reflected in the large number of novel compounds reported in the literature over the past decade [5]. Some of these agents have entered preclinical and clinical trials, and it may be expected that this number will increase in the future. This article will review some of the technical strategies that are being employed to collect and identify novel marine products with potential antitumoral properties, and will also provide a summary of the available clinical trial information of agents with promising activity.
Source: Annals of Oncology 14:1607-1615, 2003
Answers to all your Biology Questions
