Advertisement

The Deep Oceans as a Source for New Treatments for Cancer

  • William Fenical
  • James J. La Clair
  • Chambers C. Hughes
  • Paul R. Jensen
  • Susana P. Gaudêncio
  • John B. MacMillan
Conference paper

Abstract

The development of new approaches for the treatment of cancer represents one of the greatest challenges of modern-day science. Beginning in the mid-1970s with the passage of the “National Cancer Act” and the establishment of the American National Institutes of Health’s National Cancer Institute (NCI), a worldwide effort was undertaken to discover and develop new treatments for this devastating disease. Not surprisingly, one of the most important approaches to this problem was the discovery of new anticancer drugs from natural sources. Programs were developed at NCI to access new plant species from common and remote environments throughout the world, resulting in the discovery of a significant number of lead molecules, such as taxol, that ultimately became part of a primary arsenal of drugs to treat this disease. Although the ocean is 70% of the Earth’s surface and 95% of its crust, this source was not examined until later. A major effort was undertaken by NCI to collect, extract, and assay a massive number of marine plants and animals. The results were impressive, and this achievement underscored the effort to pursue marine organisms. As of 2011, more than 20 marine-derived compounds are in clinical trials for various cancers, and two drugs Yondelis®(aka Trabectedin) and Havalen®(aka Eribulin Mesylate) are currently on the market for treatment of numerous cancer subtypes [1].

Keywords

Academic Entrepreneurism Human Colon Carcinoma Cell Line Confocal Microscopic Examination American National Institute Mass Spectrometric Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

In this review, I have briefly outlined a large amount of research ongoing in my laboratory. These studies have been supported by the National Institutes of Health, National Cancer Institute under grant R37 044848.

References

  1. 1.
    Mayer AMS, Glaser KB, Cuevas C, Jacobs RS, Kem W, Little RD, McIntosh JM, Newman DJ, Potts BC, Shuster DE (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci 31:255–265PubMedCrossRefGoogle Scholar
  2. 2.
    Jensen PR, Fenical W (2000) Marine microorganisms and drug discovery: current status and future potential. In: Fusetani N (ed) Drugs from the sea. Karger, Basel, pp 6–29CrossRefGoogle Scholar
  3. 3.
    Jensen PR, Fenical W (2007) Marine actinomycete bacteria, developing a new resource for drug discovery. Nat Chem Biol 2:666–673Google Scholar
  4. 4.
    Prieto-Davó A, Fenical W, Jensen PR (2008) Actinomycete diversity in marine sediments. Aquat Microb Ecol 52:1–11CrossRefGoogle Scholar
  5. 5.
    Gontang EA, Gaudencio SP, Fenical W, Jensen PR (2010) Sequence-based secondary metabolite analysis in marine actinobacteria. Appl Environ Microbiol 76(8):2487–2499PubMedCrossRefGoogle Scholar
  6. 6.
    Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W (2003) Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinispora. Angew Chem Int Ed 42(3):355–357CrossRefGoogle Scholar
  7. 7.
    Macherla VR, Mitchell SS, Manam RR et al (2005) Structure–activity relationship studies of salinosporamide A (NPI-0052), a novel marine derived proteasome inhibitor. J Med Chem 48:3684–3687PubMedCrossRefGoogle Scholar
  8. 8.
    Potts BC, Albitar MX, Anderson KC, Baritaki S, Berkers C, Bonavida B, Chandra J, Chauhan D, Cusack JC Jr et al (2011) Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets 11:254–284CrossRefGoogle Scholar
  9. 9.
    Groll M, Huber R, Potts BCM (2006) Crystal structure of salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of ­beta-lactone ring opening and a mechanism for irreversible binding. J Am Chem Soc 128:5136–5141PubMedCrossRefGoogle Scholar
  10. 10.
    Kwon HC, Kauffman CA, Jensen PR, Fenical W (2006) Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus “Marinispora”. J Am Chem Soc 128(5):1622–1632PubMedCrossRefGoogle Scholar
  11. 11.
    Hughes CC, MacMillan JB, Gaudêncio SP, Jensen PR, Fenical W (2009) The ammosamides, structures of potent cytotoxins from a marine-derived Streptomycessp. Angew Chem Int Ed 48:725–727CrossRefGoogle Scholar
  12. 12.
    Hughes CC, MacMillan JB, Gaudêncio SP, Fenical W, La Clair JJ (2009) Covalent modification of myosin by ammosamides A and B. Angew Chem Int Ed 48:728–732CrossRefGoogle Scholar
  13. 13.
    Alexander MD, Burkart MD, Leonard MS, Portonovo P, Liang B, Ding X, Joullie MM, Gulledge BM, Aggen JB, Chamberlin AR, Sandler J, Fenical W, Cui J, Gharpure SJ, Polosukhin A, Zhang H, Evans PA, Richardson AD, Harper MK, Ireland CM, Vong BG, Brady TP, Theodorakis EA, La Clair JJ (2006) A central strategy for converting natural products into fluorescent probes. Chembiochem 7:409–416PubMedCrossRefGoogle Scholar
  14. 14.
    Lucas-Lopez C, Allingham JS, Lebl T, Lawson CP, Brenk R, Sellers JR, Rayment I, Westwood NJ (2008) The small molecule tool (S)-()-blebbistatin: novel insights of relevance to myosin inhibitor design. Org Biomol Chem 6:2076–2084PubMedCrossRefGoogle Scholar
  15. 15.
    Hughes CC, Fenical W (2010) Total synthesis of the ammosamides. J Am Chem Soc 132:2528–2529PubMedCrossRefGoogle Scholar
  16. 16.
    Hughes CC, Prieto-Davo A, Jensen PR, Fenical W (2008) The marinopyrroles, antibiotics of an unprecedented structure class from a marine Streptomycessp. Org Lett 10(4):629–631PubMedCrossRefGoogle Scholar
  17. 17.
    Hughes CC, Kauffman CA, Jensen PR, Fenical W (2010) Structures, reactivities, and antibiotic properties of the marinopyrroles A-F. J Org Chem 75:3240–3250PubMedCrossRefGoogle Scholar
  18. 18.
    Hughes CC, Yang Y-L, Liu W-T, Dorrestein PC, La Clair JJ, Fenical W (2010) Marinopyrrole A target elucidation by acyl dye transfer. J Am Chem Soc 131:12094–12096CrossRefGoogle Scholar
  19. 19.
    Singh AV, Bandi M, Raje N, Richardson P, Palladino MA, Chauhan D, Anderson KC (2011) A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells. Blood 117:5692–5700, See also: http://www.empr.com/phase-2-trial-of-plinabulin-npi-2358-for-the-treatment-of-advanced-non-small-cell-lung-cancer-nsclc/article/158324/ PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2012

Authors and Affiliations

  • William Fenical
    • 1
  • James J. La Clair
    • 2
  • Chambers C. Hughes
    • 1
  • Paul R. Jensen
    • 1
  • Susana P. Gaudêncio
    • 1
  • John B. MacMillan
    • 1
  1. 1.Center for Marine Biotechnology and Biomedicine, Scripps Institution of OceanographyUniversity of California, San DiegoLa JollaUSA
  2. 2.Xenobe Research InstituteSan DiegoUSA

Personalised recommendations