Cancer remains one of the major causes of death worldwide and the rate of people affected by it is consistently rising…who will be the next one? the solutions offered in the clinic are restricted mainly to radiotherapy and chemotherapy. Chemotherapy acts in a non specific manner over cancer cells and depresses the immune system of the patient. This often raises the need for antibiotic therapy in cancer patients treated with chemotherapy (1). New solutions in the market consist in specific antibodies, socalled “monoclonal antibodies” targeting receptors located in cancer cells. However, cancer cells normally end up relatively fast finding ways to scape, the widely described “cancer resistance” (2).
The sea has been shown to offer a wide range of natural products exhibiting anticancerous properties. There’re some indications that minerals (sea salt) obtained from the sea might act themselves as inhibitory to cancer growth (3). Other very interesting antitumoral actions are found in algae. Extracts from the microscopic green algae Chlorella have shown anticancerous properties (4, 5). Bigger in size, marine sponges contain compounds demonstrating potential antitumor activity (6). This is just an small fraction of the huge amount of data pointing out to marine substances as potential remedies for cancer. Paradoxically, despite intense initial investigation and positive results in vitro, marine compounds are not clinically available for cancer patients. To understand why, it is necessary to know the limitations of the economical profit-based process of drug development.
The anticancer products being administered to patients are molecules that have been patented and approved for clinical use. These molecules have gone through a process of drug development, which include preclinical studies in animals and clinical studies in patients. But, why are pharmaceutical drugs patented? Patenting guarantees that the laboratory putting the drug into the market will have exclusivity in the selling and benefits of the new product. This is done according to the TRIPS (Trade-Related Aspects of Intellectual Property Rights) agreement, so that the available term of protection must expire no earlier than 20 years from the date of filing the patent application (7). Another important issue is that, according to the World Trade Organization, natural products generally can not be patented. Thus, based of the economic profit, there are many limitations to the possibility of having efficient anticancer remedies derived from the sea, available for cancer patients:
1) Clinical research is mainly funded by pharmaceutical companies.
2) Only products which have been patented will normally undergo clinical trials in humans.
3) Normally only single molecules can be patented.
4) If the molecule looses its therapeutical properties while being isolated from its natural milieu, or due to chemical modifications, it is likely to be discarded as not profitable, regardless of its potential therapeutical activity.
5) If this molecule can not be synthesized in vitro in an industrial manner, it is also likely to be rejected.
Therefore, based on the rule of economic profit, the possibility of marine products to be used in the clinic as anticancer compounds is still very remote. Indeed, experts have described that researchers, including the ones within academia, might undertake studies only on the basis of whether they can get industry funding, not whether the studies are scientifically important (8). Meanwhile, according to Marcia Angell, Dr. in Medicine and exeditor in chief of New England Journal of Medicine -the best rated journal in the field of medicine-, only one fourth of new approved drugs offer advantages with respect to the ones which are already in the market (9). In a recent article published in the journal Nature Medicine, it was claimed that some new developed drugs, approved for the treatment of cancer, showed improvements of life span of only less than two weeks (10). Although accurate scientific information is needed for doctors to choose which drug to prescribe to their patients, independent information is lacking, as continuous medical education is mainly financed by pharmaceutical companies. An ideal solution for this situation would be to favour medical education and clinical research independent of pharmaceutical industry, supported by public funding, as a part of public healthcare expenses. This way, healthcare expenses of the country would limit the financing of drugs with none or very little added benefit and instead, successfully invest in clinical research of compounds that, even if non economically profitable, show promising potential benefit for human health.
While the sea is waiting for us to apply its vast array of anticancer products, it has been reported the appearance of cancer in wildlife marine species that were so far free of this devastating disease. According to experts, human action is likely to be blamed. Plastic concentrations in the sea are increasing tremendously. In the past there were only big fragments of plastic, but corrosion and fragmentation of those pieces has led to the appearance of very small particles, which are easily eaten by marine organisms. In the meantime, compounds we know little of enter the marine and terrestrial food chain, ultimately reaching the human body (11). An additional reason, among many others, to keep our crystalline source of life, a sea of anticancer remedies, free of human-action derived debris and contamination.
1. Cullen M, Steven N, Billingham L, Gaunt C, Hastings M, Simmonds P, Stuart N, Rea D, Bower M, Fernando I, Huddart R, Gollins S, Stanley A 2005 Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 353:988-99
2. Reslan L, Dalle S, Dumontet C 2009 Understanding and circumventing resistance to anticancer monoclonal antibodies. MAbs 1:222-229
3. Ghoneum M, Gollapudi S 2009 Susceptibility of the human LNCaP prostate cancer cells to the apoptotic effect of marina crystal minerals (MCM) in vitro. Oncol Rep 22:155-159
4. Cha KH, Koo SY, Lee DU 2008 Antiproliferative effects of carotenoids extracted from Chlorella ellipsoidea and Chlorella vulgaris on human colon cancer cells. J Agric Food Chem 56:10521-10526
5. Ramos AL, Torello CO, Queiroz ML 2010 Chlorella vulgaris modulates immunomyelopoietic activity and enhances the resistance of tumor-bearing mice. Nutr Cancer 62:1170-1180
6. Paleari L, Trombino S, Falugi C, Gallus L, Carlone S, Angelini C, Sepcic K, Turk T, Faimali M, Noonan DM, Albini A 2006 Marine sponge-derived polymeric alkylpyridinium salts as a novel tumor chemotherapeutic targeting the cholinergic system in lung tumors. Int J Oncol 29:1381-1388
7. http://www.wto.org/english/tratop_e/trips_e/pharma_ato186_e.htm
8. Angell M 2000 Is academic medicine for sale? N Engl J Med 342:1516-1518
9. Angell M 2003 The Truth About the Drug Companies: How They Deceive Us and What to Do About It. Book
10. Hoag H 2011 Cancer drugs should add months, not weeks, say experts. Nat Med 17:7
11. Erren T, Zeuss D, Steffany F, Meyer-Rochow B 2009 Increase of wildlife cancer: an echo of plastic pollution? Nat Rev Cancer 9:842; author reply 842
Autor: Blanca Rubi, PhD
