Abstract
Natural products from marine invertebrates and microbes from terrestrial (and marine) sources together with higher plants have been an important source of many clinically useful anticancer agents. Over 60% of the current anticancer drugs have their origin in one way or another from natural sources. Some important examples include the vinca alkaloids, camptothecin derivatives, and taxanes. This chapter will briefly cover older agents where new findings have been published but will emphasize current promising new agents which are in clinical use and development, based on activity against cancer-related targets. These compounds may have been developed from targeted or phenotypic screening programs, and examples will be given from each approach. Then the importance of multidisciplinary collaboration in the generation and optimization of novel molecular leads from natural product sources will be discussed, with examples chosen to demonstrate how chemical and biochemical strategies were used to improve their biological effects.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agatsuma T (2017) Development of new ADC technology with topoisomerase I inhibitor. Yakugaku Zasshi 137:545–550
Andrejauskas-Buchdunger E, Reganass U (1992) Differential inhibition of the epidermal growth factor-, platelet derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251. Cancer Res 52:5353–5358
Awada A, Bondarenko IN, Bonneterre J et al (2014) A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC). Ann Oncol 25:824–831
Basmadjian C, Zhao Q, Djehal A et al (2014) Cancer wars: natural products strike back. Front Chem 2:20
Bebbington MWP (2017) Natural product analogues: towards a blueprint for analogue-focused synthesis. Chem Soc Rev 46:5059–5109
Bertin MJ, Schwartz SL, Lee J et al (2015) Spongosine production by a Vibrio harveyi strain associated with the sponge Tectitethya crypta. J Nat Prod 78:493–499
Black J, Menderes G, Bellone S et al (2016) SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows antitumor activity in uterine serous carcinoma with HER2/Neu expression. Mol Cancer Ther 15:1900–1909
Chan SY, Gordon AN, Coleman RE et al (2003) A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinum-sensitive recurrent epithelial ovarian carcinoma. Cancer Immunol Immunother 52:243–248
Cragg GM, Newman DJ (2014) Natural products as sources of new anticancer agents. In: Feliciano AS, Filho VC (eds) Descoberta, Desenho e Desenvolvivmento de Novos Agentes Anticancer no Ambito do Programa Iberoamericano CYTED. Editoria Univali, Itajai, pp 67–118
Cragg GM, Pezzuto JM (2016) Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract 25:41–59
Damelin M, Bankovich A, Park A et al (2015) Anti-EFNA4 calicheamicin conjugates effectively target triple-negative breast and ovarian tumor-initiating cells to result in sustained tumor regressions. Clin Cancer Res 21:4165–4173
Davis AM, Tinker AV, Friedlander M (2014) “Platinum resistant” ovarian cancer: what is it, who to treat and how to measure benefit? Gynecol Oncol 133:624–631
Elgersma RC, Coumans RG, Huijbregts T et al (2015) Design, synthesis, and evaluation of linker-duocarmycin payloads: toward selection of HER2-targeting antibody-drug conjugate SYD985. Mol Pharm 12:1813–1835
Galal A, El-Bakly WM, El-Demedash E (2016) Selective A3 adenosine receptor agonist protects against doxorubicin-induced cardiotoxicity. Cancer Chemother Pharmacol 77:309–322
Giddings LA, Newman DJ (2015) Bioactive compounds from extremophiles, genomic studies, biosynthetic gene clusters, and new dereplication methods. In: Tiquia-Arashiro SM, Mormile M (eds) Extremophilic bacteria, Springer briefs in microbiology. Springer, Heidelberg, pp 1–58
Giddings LA, Newman DJ (2017) Microbial involvement in the production of natural products by plants, marine invertebrates and other organisms. In: Atta-ur-Rahman (ed) Frontiers in natural product chemistry, vol 3. Bentham, Karachi, pp 1–64
Gottfried K, Klar U, Platzek J et al (2015) Biocatalysis at work: applications in the development of Sagopilone. ChemMedChem 10:1240–1248
Graybill WS, Coleman RL (2016) Folate receptor-targeted therapeutics for ovarian cancer. Drugs Future 41:137–143
Herzog TJ, Kutarska E, Bidzińsk M et al (2016) Adverse event profile by folate receptor status for vintafolide and pegylated liposomal doxorubicin in combination, versus pegylated liposomal doxorubicin alone, in platinum-resistant ovarian cancer: Exploratory analysis of the Phase II PRECEDENT trial. Int J Gynecol Cancer 26:1580–1585
Huang M, Gao H, Chen Y et al (2007) Chimmitecan, a novel 9-substituted camptothecin, with improved anticancer pharmacologic profiles in vitro and in vivo. Clin Cancer Res 13:1298–1307
Huang G, Wang H, Yang LX (2010) Enhancement of radiation-induced DNA damage and inhibition of its repair by a novel camptothecin analog. Anticancer Res 30:937–944
Joerger M, Hess D, Delmonte A et al (2015) Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968). Br J Clin Pharmacol 80:128–138
Jones RP, Malik HZ, Fenwick SW et al (2016) PARAGON II – a single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer. Eur J Surg Oncol 42:1866–1872
Kusari S, Lamsho M, Kusari P et al (2014) Endophytes are hidden producers of maytansine in Putterlickia roots. J Nat Prod 77:2577–2584
Kusari P, Kusari S, Eckelmann D et al (2016) Cross-species biosynthesis of maytansine in Maytenus serrata. RSC Adv 6:10011–10016
Lambert JM (2012) Drug-conjugated antibodies for the treatment of cancer. Br J Clin Pharmacol 76:248–262
Lee KW, Lee KH, Zang DY et al (2015) Phase I/II study of weekly Oraxol for the second-line treatment of patients with metastatic or recurrent gastric cancer. Oncologist 20(8):896–897
Li JY, Perry SR, Muniz-Medina V et al (2016) A biparatopic HER2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy. Cancer Cell 29(1):117–129
Liu X, Kantarjian H, Plunkett W (2012) Sapacitabine for cancer. Expert Opin Investig Drugs 21(4):541–555
Mantaj J, Jackson PJM, Rahman KM et al (2017) From anthramycin to pyrrolobenzodiazepine (PBD) containing antibody-drug conjugates (ADCs). Angew Chem Int Ed Engl 56(2):462–488
Martín MJ, Coello L, Fernández R et al (2013) Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds. J Am Chem Soc 135(27):10164–10171
Montalban-Bravo G, Garcia-Manero G (2015) Novel drugs for older patients with acute myeloid leukemia. Leukemia 29(4):760–769
Nakada T, Masuda T, Naito H et al (2016) Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorg Med Chem Lett 26:1542–1545
Newman DJ (2008) Natural products as leads to potential drugs: An old process or the new hope for drug discovery? J Med Chem 51:2589–2599
Newman DJ (2016) Predominately uncultured microbes as sources of bioactive agents. Front Microbiol 7:1832
Newman DJ (2017) Recent advances in screening and identification of novel biologically active natural compounds. F1000 Fac Rev 6:783
Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75(3):311–335
Newman DJ, Cragg GM (2014) Making sense of structures by utilizing Mother Nature’s chemical libraries as leads to potential drugs. In: Osbourn A, Goss RJ (eds) Natural products: discourse, diversity and design. Wiley, New York, pp 397–411
Newman DJ, Cragg GM (2015) Endophytic and epiphytic microbes as “sources” of bioactive agents. Front Chem 3:34
Newman DJ, Cragg GM (2016a) Natural product scaffolds of value in medicinal chemistry. In: Brase S (ed) Privileged scaffolds in medicinal chemistry. Royal Society of Chemistry, London, pp 348–378
Newman DJ, Cragg GM (2016b) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79(3):629–661
Newman DJ, Cragg GM (2017) Current status of marine-derived compounds as warheads in anti-tumor drug candidates. Mar Drugs 15(4) 99.
Newman DJ, Cragg GM, Snader KM (2000) The influence of natural products upon drug discovery. Nat Prod Rep 17(3):215–234
Newman DJ, Cragg GM, Kingston DGI (2015) Natural products as pharmaceuticals and sources for lead structures. In: Aldous D, Rognan D, Raboisson P et al (eds) The practice of medicinal chemistry, 4th edn. Elsevier, Amsterdam, pp 102–138
Pera B, Barasoain I, Pantazopoulou A et al (2013) New interfacial microtubule inhibitors of marine origin, PM050489/PM060184, with potent antitumor activity and a distinct mechanism. ACS Chem Biol 8(9):2084–2094
Santamaría NG, Robles CM, Giraudon C et al (2016) Lurbinectedin specifically triggers the degradation of phosphorylated RNA polymerase II and the formation of DNA breaks in cancer cells. Mol Cancer Ther 15(10):2399–2412
Shi J, Kantoff PW, Wooster R et al (2017) Cancer nanomedicine: Progress, challenges and opportunities. Nat Rev Cancer 17(1):20–37
Wakimoto T, Egami Y, Nakashima Y et al (2014) Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont. Nat Chem Biol 10(8):648–655
Wicki A, Ritschard R, Loesch U et al (2015) Large-scale manufacturing of GMP-compliant anti-EGFR targeted nanocarriers: Production of doxorubicin-loaded ant-EGFR-immunoliposomes for a first-in-man clinical trial. Int J Pharm 484(1–2):8–15
Wilson MC, Mori T, Ruckert C et al (2014) An environmental bacterial taxon with a large and distinct metabolic repertoire. Nature 506(7486):58–62
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Cragg, G.M., Newman, D.J. (2018). Natural Products as Sources of Anticancer Agents: Current Approaches and Perspectives. In: Cechinel Filho, V. (eds) Natural Products as Source of Molecules with Therapeutic Potential. Springer, Cham. https://doi.org/10.1007/978-3-030-00545-0_8
Download citation
DOI: https://doi.org/10.1007/978-3-030-00545-0_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-00544-3
Online ISBN: 978-3-030-00545-0
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)