Finding chemo: The search for marine-based pharmaceutical drugs active against cancer

Journal of Pharmacy and Pharmacology

Volumn 65, Issue 9, 2013, Pages 1280-1301

  Indumathy, Sivanjah ^a   Dass, Crispin R ^b  

^a VICTORIA UNIVERSITY   (Australia)

^b CURTIN UNIVERSITY   (Australia)

Author keywords

apoptosis; cancer; drug; growth arrest; marine

Indexed keywords

ANTINEOPLASTIC AGENT; ASCIDIDEMIN; BRYOSTATIN 1; CEPHALOSTATIN 1; CRYPTOSPHAEROLIDE; CYTARABINE; DACINOSTAT; DAUNORUBICIN; DEHYDRODIDEMNIN B; DEXAMETHASONE; DIDEOXYPETROSYNOL A; DOLASTATIN; ERIBULIN; FASCAPLYSIN; FUCOXANTHINOL; ICRININ 1; JASPAMIDE; JASPINE B; LAMELLARIN D; MITOXANTRONE; NAAMIDINE A; ONNAMIDE A; PM 00104; PORPHYRAN; SALINOSPORAMIDE A; SOMOCYSTINAMIDE A; SPONGISTATIN 1; THEOPEDRIN B; TRABECTEDIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZALYPSIS;

ACUTE GRANULOCYTIC LEUKEMIA; ADVANCED CANCER; ALOPECIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ASTHENIA; B CELL LEUKEMIA; BLOOD TOXICITY; BREAST CANCER; CANCER CELL; CANCER SURVIVAL; CELL CYCLE ARREST; CENTRAL NERVOUS SYSTEM DISEASE; CONSTIPATION; CONTINUOUS INFUSION; CYTOLOGY; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG FEVER; DRUG MARKETING; DRUG MEGADOSE; DRUG POTENCY; DRUG RESEARCH; DRUG SAFETY; DRUG SCREENING; DRUG STRUCTURE; DRUG TOLERABILITY; ENDOMETRIUM CARCINOMA; FATIGUE; GROWTH INHIBITION; HUMAN; HYPOTENSION; INFECTION; LEUKEMIA REMISSION; LIPOSARCOMA; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MARINE ENVIRONMENT; MELANOMA; MESOTHELIOMA; MULTIPLE MYELOMA; MYALGIA; NAUSEA; NEUROMUSCULAR DISEASE; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY ADENOCARCINOMA; OVARY CANCER; OVARY CARCINOMA; OVERALL SURVIVAL; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHLEBITIS; PLASMACYTOMA; PROGRESSION FREE SURVIVAL; PROTEIN SECRETION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; REVIEW; SARCOMA; SIGNAL TRANSDUCTION; SKIN TOXICITY; SOFT TISSUE CANCER; SOLID TUMOR; THROMBOCYTOPENIA; UROGENITAL TRACT CANCER; VOMITING;

EID: 84881394276     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/jphp.12097     Document Type: Review

References (145)

1. Hanahan D, Weinberg RA,. The hallmarks of cancer. Cell 2000; 1: 57-70. (Pubitemid 30046295)
2. Hanahan D, Weinberg RA,. Hallmarks of cancer: the next generation. Cell 2011; 5: 646-674.
3. Siddiqa A, Marciniak R,. Targeting the hallmarks of cancer. Cancer Biol Ther 2008; 5: 740-741.
4. Speirs CK, et al. Harnessing the cell death pathway for targeted cancer treatment. Am J Cancer Res 2011; 1: 43-61.
5. Rufini A, Melino G,. Cell death pathology: the war against cancer. Biochem Biophys Res Commun 2011; 3: 445-450.
6. Mathiasen IS, Jaattela M,. Triggering caspase-independent cell death to combat cancer. Trends Mol Med 2002; 5: 212-220. (Pubitemid 34493638)
7. D'Incalci M, Galmarini CM,. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther 2010; 8: 2157-2163.
8. Williams GH, Stoeber K,. The cell cycle and cancer. J Pathol 2012; 2: 352-364.
9. Henley SA, Dick FA,. The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle. Cell Div 2012; 1: 10.
10. Giamas G, et al. Kinases as targets in the treatment of solid tumors. Cell Signal 2010; 7: 984-1002.
11. McCubrey JA, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007; 8: 1263-1284. (Pubitemid 47125967)
12. McCubrey JA, et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul 2006; 46: 249-279. (Pubitemid 44301348)
13. Santarpia L, et al. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 1: 103-119.
14. Weston CR, Davis RJ,. The JNK signal transduction pathway. Curr Opin Cell Biol 2007; 2: 142-149. (Pubitemid 46386399)
15. Davis RJ,. Signal transduction by the JNK group of MAP kinases. Cell 2000; 2: 239-252.
16. Vlahopoulos S, Zoumpourlis VC,. JNK: a key modulator of intracellular signaling. Biochemistry 2004; 8: 844-854.
17. Hennessy BT, et al. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005; 12: 988-1004.
18. Kok K, et al. Regulation of phosphoinositide 3-kinase expression in health and disease. Trends Biochem Sci 2009; 3: 115-127.
19. Ogawara Y, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem 2002; 24: 21843-21850. (Pubitemid 34952337)
20. Mayo LD, Donner DB,. The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends Biochem Sci 2002; 9: 462-467. (Pubitemid 35246255)
21. Gorin MA, Pan Q,. Protein kinase C epsilon: an oncogene and emerging tumor biomarker. Mol Cancer 2009; 8: 9.
22. Basu A, Sivaprasad U,. Protein kinase C epsilon makes the life and death decision. Cell Signal 2007; 8: 1633-1642. (Pubitemid 46935437)
23. Kerr JF, et al. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 4: 239-257.
24. Lin X, et al. Targeting cellular proapoptotic molecules for developing anticancer agents from marine sources. Curr Drug Targets 2010; 6: 708-715.
25. Hellwig CT, et al. The molecular machinery regulating apoptosis signal transduction and its implication in human physiology and pathophysiologies. Curr Mol Med 2011; 1: 31-47.
26. Giam M, et al. BH3-only proteins and their roles in programmed cell death. Oncogene 2008; 27: S128-S136.
27. Chipuk JE, Green DR,. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 2008; 4: 157-164.
28. Ola MS, et al. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 2011; 1-2: 41-58.
29. Zhao J, et al. Targeting p53 as a therapeutic strategy in sensitizing TRAIL-induced apoptosis in cancer cells. Cancer Lett 2012; 1: 8-23.
30. Olsson M, Zhivotovsky B,. Caspases and cancer. Cell Death Differ 2011; 9: 1441-1449.
31. Singh R, et al. Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem 2008; 6: 603-617.
32. Sima P, Vetvicka V,. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata. World J Clin Oncol 2011; 11: 355-361.
33. Adrian TE,. Novel marine-derived anti-cancer agents. Curr Pharm Des 2007; 33: 3417-3426. (Pubitemid 350201675)
34. Imhoff JF, et al. Bio-mining the microbial treasures of the ocean: new natural products. Biotechnol Adv 2011; 5: 468-482.
35. Sima P, Vetvicka V,. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Bryozoa, Mollusca, Echinodermata and Urochordata. World J Clin Oncol 2011; 11: 362-366.
36. Kinghorn AD, et al. Discovery of natural product anticancer agents from biodiverse organisms. Curr Opin Drug Discov Devel 2009; 2: 189-196.
37. Tan ML, et al. Cancer, chitosan nanoparticles and catalytic nucleic acids. J Pharm Pharmacol 2009; 1: 3-12.
38. Penna F, et al. Caspase 2 activation and ER stress drive rapid jurkat cell apoptosis by clofibrate. PLoS One 2012; 9: e45327.
39. Backway KL, et al. Relationships between the mitochondrial permeability transition and oxidative stress during ara-C toxicity. Cancer Res 1997; 12: 2446-2451. (Pubitemid 27255905)
40. Hu ZB, et al. Post-transcriptional regulation of bcl-2 in acute myeloblastic leukemia: significance for response to chemotherapy. Leukemia 1996; 3: 410-416.
41. Romano MF, et al. Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NF-kappa B/Rel- specific decoy oligodeoxynucleotides. Gene Ther 2000; 14: 1234-1237. (Pubitemid 30488770)
42. Malumbres M, Barbacid M,. Cell cycle kinases in cancer. Curr Opin Genet Dev 2007; 1: 60-65. (Pubitemid 46109297)
43. Xu Y, et al. Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism. Anticancer Res 2009; 12: 5103-5109.
44. Gajate C, et al. Differential cytostatic and apoptotic effects of ecteinascidin-743 in cancer cells. Transcription-dependent cell cycle arrest and transcription-independent JNK and mitochondrial mediated apoptosis. J Biol Chem 2002; 44: 41580-41589. (Pubitemid 35257462)
45. Jordan MA, et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther 2005; 7: 1086-1095. (Pubitemid 41079102)
46. Kuznetsov G, et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res 2004; 16: 5760-5766. (Pubitemid 39095575)
47. Carmody RJ, Cotter TG,. Oxidative stress induces caspase-independent retinal apoptosis in vitro. Cell Death Differ 2000; 3: 282-291. (Pubitemid 30192977)
48. Laibson PR, et al. Ara-A and IDU therapy of human superficial herpetic keratitis. Invest Ophthalmol 1975; 10: 762-763.
49. Leal JF, et al. Molecular pharmacology and antitumor activity of Zalypsis in several human cancer cell lines. Biochem Pharmacol 2009; 2: 162-170.
50. Ocio EM, et al. Zalypsis: a novel marine-derived compound with potent antimyeloma activity that reveals high sensitivity of malignant plasma cells to DNA double-strand breaks. Blood 2009; 16: 3781-3791.
51. Colado E, et al. Zalypsis has in vitro activity in acute myeloid blasts and leukemic progenitor cells through the induction of a DNA damage response. Haematologica 2011; 5: 687-695.
52. Ahn KS, et al. Salinosporamide A (NPI-0052) potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through down-modulation of NF-kappaB regulated gene products. Blood 2007; 7: 2286-2295.
53. Chauhan D, et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 2005; 5: 407-419. (Pubitemid 41579835)
54. B CP, et al. Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets 2011; 3: 254-284.
55. Miller CP, et al. Specific and prolonged proteasome inhibition dictates apoptosis induction by marizomib and its analogs. Chem Biol Interact 2011; 1: 58-68.
56. Miller CP, et al. Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cells. Blood 2009; 18: 4289-4299.
57. Millward M, et al. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Invest New Drugs 2012; 30: 2303-2317.
58. Singh AV, et al. Pharmacodynamic and efficacy studies of the novel proteasome inhibitor NPI-0052 (marizomib) in a human plasmacytoma xenograft murine model. Br J Haematol 2010; 4: 550-559.
59. Chauhan D, et al. A novel proteasome inhibitor NPI-0052 as an anticancer therapy. Br J Cancer 2006; 8: 961-965. (Pubitemid 44606819)
60. von Schwarzenberg K, Vollmar AM,. Targeting apoptosis pathways by natural compounds in cancer: marine compounds as lead structures and chemical tools for cancer therapy. Cancer Lett 2013; 332: 295-303.
61. Schumacher M, et al. Gold from the sea: marine compounds as inhibitors of the hallmarks of cancer. Biotechnol Adv 2011; 5: 531-547.
62. Oh H, et al. Cryptosphaerolide, a cytotoxic Mcl-1 inhibitor from a marine-derived ascomycete related to the genus Cryptosphaeria. J Nat Prod 2010; 5: 998-1001.
63. Michels J, et al. Mcl-1. Int J Biochem Cell Biol 2005; 2: 267-271. (Pubitemid 39330187)
64. Catassi A, et al. Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells. Cell Mol Life Sci 2006; 19-20: 2377-2386. (Pubitemid 44653047)
65. Schneiders UM, et al. BH3-only proteins Mcl-1 and Bim as well as endonuclease G are targeted in spongistatin 1-induced apoptosis in breast cancer cells. Mol Cancer Ther 2009; 10: 2914-2925.
66. Schyschka L, et al. Spongistatin 1: a new chemosensitizing marine compound that degrades XIAP. Leukemia 2008; 9: 1737-1745.
67. Rudy A, et al. Role of Smac in cephalostatin-induced cell death. Cell Death Differ 2008; 12: 1930-1940.
68. Dirsch VM, et al. Cephalostatin 1 selectively triggers the release of Smac/DIABLO and subsequent apoptosis that is characterized by an increased density of the mitochondrial matrix. Cancer Res 2003; 24: 8869-8876. (Pubitemid 38064067)
69. Muller IM, et al. Cephalostatin 1 inactivates Bcl-2 by hyperphosphorylation independent of M-phase arrest and DNA damage. Mol Pharmacol 2005; 5: 1684-1689. (Pubitemid 40594168)
70. Maki A, et al. The bcl-2 and p53 oncoproteins can be modulated by bryostatin 1 and dolastatins in human diffuse large cell lymphoma. Anticancer Drugs 1995; 3: 392-397.
71. Sato M, et al. A natural peptide, dolastatin 15, induces G2/M cell cycle arrest and apoptosis of human multiple myeloma cells. Int J Oncol 2007; 6: 1453-1459.
72. Piplani H, et al. Up-regulation of p53 and mitochondrial signaling pathway in apoptosis by a combination of COX-2 inhibitor, celecoxib and dolastatin 15, a marine mollusk linear peptide in experimental colon carcinogenesis. Mol Carcinog 2012. doi 10.1002/mc.21925
73. Piplani H, et al. Dolastatin 15, a mollusk linear peptide, and Celecoxib, a selective cyclooxygenase-2 inhibitor, prevent preneoplastic colonic lesions and induce apoptosis through inhibition of the regulatory transcription factor NF-kappaB and an inflammatory protein, iNOS. Eur J Cancer Prev 2012; 21: 511-522.
74. Watanabe J, et al. Induction of apoptosis in human cancer cells by TZT-1027, an antimicrotubule agent. Apoptosis 2000; 4: 345-353.
75. Yamamoto K, et al. Fucoxanthin and its deacetylated product, fucoxanthinol, induce apoptosis of primary effusion lymphomas. Cancer Lett 2011; 2: 225-234.
76. Konishi I, et al. Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells. Comp Biochem Physiol C Toxicol Pharmacol 2006; 1-2: 53-59. (Pubitemid 43142054)
77. Dirsch VM, et al. Apoptosis signaling triggered by the marine alkaloid ascididemin is routed via caspase-2 and JNK to mitochondria. Oncogene 2004; 8: 1586-1593. (Pubitemid 38406521)
78. Choi HJ, et al. Ircinin-1 induces cell cycle arrest and apoptosis in SK-MEL-2 human melanoma cells. Mol Carcinog 2005; 3: 162-173. (Pubitemid 41552749)
79. Schwarz K, et al. The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic progenitor cells. Leuk Res 2011; 1: 119-125.
80. Wang S, et al. Activation of mitochondrial pathway is crucial for tumor selective induction of apoptosis by LAQ824. Cell Cycle 2006; 15: 1662-1668. (Pubitemid 44285253)
81. LaBarbera DV, et al. The marine alkaloid naamidine A promotes caspase-dependent apoptosis in tumor cells. Anticancer Drugs 2009; 6: 425-436.
82. Copp BR, et al. Naamidine A is an antagonist of the epidermal growth factor receptor and an in vivo active antitumor agent. J Med Chem 1998; 20: 3909-3911. (Pubitemid 28447318)
83. James RD, et al. Naamidine A intensifies the phosphotransferase activity of extracellular signal-regulated kinases causing A-431 cells to arrest in G1. Mol Cancer Ther 2003; 8: 747-751.
84. Lee KH, et al. Inhibition of protein synthesis and activation of stress-activated protein kinases by onnamide A and theopederin B, antitumor marine natural products. Cancer Sci 2005; 6: 357-364.
85. Kluza J, et al. Cancer cell mitochondria are direct proapoptotic targets for the marine antitumor drug lamellarin D. Cancer Res 2006; 6: 3177-3187.
86. Ballot C, et al. Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D. Mol Cancer Ther 2009; 12: 3307-3317.
87. Ballot C, et al. Inhibition of mitochondrial respiration mediates apoptosis induced by the anti-tumoral alkaloid lamellarin D. Apoptosis 2010; 7: 769-781.
88. Facompre M, et al. Lamellarin D: a novel potent inhibitor of topoisomerase I. Cancer Res 2003; 21: 7392-7399. (Pubitemid 37413481)
89. Kwon MJ, Nam TJ,. Porphyran induces apoptosis related signal pathway in AGS gastric cancer cell lines. Life Sci 2006; 20: 1956-1962.
90. Cioca DP, Kitano K,. Induction of apoptosis and CD10/neutral endopeptidase expression by jaspamide in HL-60 line cells. Cell Mol Life Sci 2002; 8: 1377-1387.
91. Odaka C, et al. Jasplakinolide induces apoptosis in various transformed cell lines by a caspase-3-like protease-dependent pathway. Clin Diagn Lab Immunol 2000; 6: 947-952. (Pubitemid 32244495)
92. Park C, et al. Suppression of U937 human monocytic leukemia cell growth by dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., via induction of Cdk inhibitor p16 and down-regulation of pRB phosphorylation. Oncol Rep 2006; 1: 171-176.
93. Choi HJ, et al. Induction of apoptosis by dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., in human skin melanoma cells. Int J Mol Med 2004; 6: 1091-1096.
94. Salma Y, et al. The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism. Biochem Pharmacol 2009; 5: 477-485.
95. Yoo H, et al. Pachastrissamine from Pachastrissa sp. inhibits melanoma cell growth by dual inhibition of Cdk2 and ERK-mediated FOXO3 downregulation. Phytother Res 2012; 26: 1927-1933.
96. Yoshimitsu Y, et al. Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C. Bioorg Med Chem 2011; 18: 5402-5408.
97. Wrasidlo W, et al. The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8. Proc Natl Acad Sci U S A 2008; 7: 2313-2318. (Pubitemid 351520510)
98. Kong CS, et al. Induction of apoptosis by phloroglucinol derivative from Ecklonia Cava in MCF-7 human breast cancer cells. Food Chem Toxicol 2009; 7: 1653-1658.
99. Yan X, et al. Fascaplysin exert anti-tumor effects through apoptotic and anti-angiogenesis pathways in sarcoma mice model. Eur J Pharm Sci 2011; 4: 251-259.
100. Soni R, et al. Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. Biochem Biophys Res Commun 2000; 3: 877-884.
101. Lu XL, et al. [Anti-proliferation of human cervical cancer HeLa cell line by fascaplysin through apoptosis induction]. Yao Xue Xue Bao 2009; 9: 980-986.
102. Jin JO, et al. Differential effects of triterpene glycosides, frondoside A and cucumarioside A2-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells. FEBS Lett 2009; 4: 697-702.
103. Pimentel AA, et al. The marine sponge toxin agelasine B increases the intracellular Ca(2+) concentration and induces apoptosis in human breast cancer cells (MCF-7). Cancer Chemother Pharmacol 2012; 1: 71-83.
104. Schumacher M, et al. Heteronemin, a spongean sesterterpene, inhibits TNF alpha-induced NF-kappa B activation through proteasome inhibition and induces apoptotic cell death. Biochem Pharmacol 2010; 4: 610-622.
105. Yuan J, et al. A novel adriamycin analogue derived from marine microbes induces apoptosis by blocking Akt activation in human breast cancer cells. Mol Med 2011; 2: 261-265.
106. Ning X, et al. A novel anti-tumor protein extracted from Meretrix meretrix Linnaeus induces cell death by increasing cell permeability and inhibiting tubulin polymerization. Int J Oncol 2009; 4: 805-812.
107. Russo P, et al. From the sea to anticancer therapy. Curr Med Chem 2011; 23: 3551-3562.
108. Bruserud O, et al. Use of marine toxins in combination with cytotoxic drugs for induction of apoptosis in acute myelogenous leukaemia cells. Expert Opin Biol Ther 2002; 2: 197-210. (Pubitemid 34464822)
109. Qi L, et al. In vitro and in vivo suppression of hepatocellular carcinoma growth by chitosan nanoparticles. Eur J Cancer 2007; 1: 184-193. (Pubitemid 46054473)
110. Mayer RJ, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 1994; 14: 896-903. (Pubitemid 24299870)
111. Dillman RO, et al. A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of cancer and leukemia group B. Blood 1991; 10: 2520-2526.
112. Lowenberg B, et al. Cytarabine dose for acute myeloid leukemia. N Engl J Med 2011; 11: 1027-1036.
113. van Kesteren C, et al. Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine origin. Anticancer Drugs 2003; 7: 487-502. (Pubitemid 37083154)
114. Vincenzi B, et al. Wide-spectrum characterization of trabectedin: biology, clinical activity and future perspectives. Pharmacogenomics 2010; 6: 865-878.
115. Pangestuti R, Kim SK,. Neuroprotective properties of chitosan and its derivatives. Mar Drugs 2010; 7: 2117-2128.
116. Ghielmini M, et al. In vitro schedule-dependency of myelotoxicity and cytotoxicity of ecteinascidin 743 (ET-743). Ann Oncol 1998; 9: 989-993. (Pubitemid 28496708)
117. Bruynzeel AM, et al. Caspase-dependent and -independent suppression of apoptosis by monoHER in Doxorubicin treated cells. Br J Cancer 2007; 3: 450-456. (Pubitemid 46215216)
118. Broker LE, et al. Cell death independent of caspases: a review. Clin Cancer Res 2005; 9: 3155-3162. (Pubitemid 40627860)
119. Valoti G, et al. Ecteinascidin-743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts. Clin Cancer Res 1998; 8: 1977-1983. (Pubitemid 28369184)
120. Constantinou C, et al. Caspase-independent pathways of programmed cell death: the unraveling of new targets of cancer therapy? Curr Cancer Drug Targets 2009; 6: 717-728.
121. Pradelli LA, et al. Mitochondrial control of caspase-dependent and -independent cell death. Cell Mol Life Sci 2010; 10: 1589-1597.
122. Kim R, et al. Regulation and interplay of apoptotic and non-apoptotic cell death. J Pathol 2006; 3: 319-326. (Pubitemid 43210518)
123. Villalona-Calero MA, et al. A phase I and pharmacokinetic study of ecteinascidin-743 on a daily x 5 schedule in patients with solid malignancies. Clin Cancer Res 2002; 1: 75-85. (Pubitemid 34101461)
124. Forouzesh B, et al. Phase I and pharmacokinetic study of trabectedin as a 1- or 3-hour infusion weekly in patients with advanced solid malignancies. Clin Cancer Res 2009; 10: 3591-3599.
125. Chu Q, et al. Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. Clin Cancer Res 2010; 9: 2656-2665.
126. Dass CR, et al. Chitosan microparticles encapsulating PEDF plasmid demonstrate efficacy in an orthotopic metastatic model of osteosarcoma. Biomaterials 2007; 19: 3026-3033. (Pubitemid 46560874)
127. Towle MJ, et al. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res 2001; 3: 1013-1021. (Pubitemid 32174419)
128. Goel S, et al. A phase I study of eribulin mesylate (E7389), a mechanistically novel inhibitor of microtubule dynamics, in patients with advanced solid malignancies. Clin Cancer Res 2009; 12: 4207-4212.
129. Tan AR, et al. Phase I study of eribulin mesylate administered once every 21 days in patients with advanced solid tumors. Clin Cancer Res 2009; 12: 4213-4219.
130. Cortes J, et al. Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. J Clin Oncol 2010; 25: 3922-3928.
131. Vahdat LT, et al. Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2009; 18: 2954-2961.
132. Cortes J, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011; 9769: 914-923.
133. Twelves C, et al. Phase III trials of eribulin mesylate (E7389) in extensively pretreated patients with locally recurrent or metastatic breast cancer. Clin Breast Cancer 2010; 2: 160-163.
134. Sumpter K, et al. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer 2005; 11: 1976-1983. (Pubitemid 40897418)
135. Miller KD, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 4: 792-799. (Pubitemid 46224178)
136. Miki H, et al. Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol 2012; 4: 1020-1028.
137. Dumez H, et al. Phase II study of biweekly plitidepsin as second-line therapy for advanced or metastatic transitional cell carcinoma of the urothelium. Mar Drugs 2009; 7: 451-463.
138. Mateos MV, et al. Phase II clinical and pharmacokinetic study of plitidepsin 3-hour infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma. Clin Cancer Res 2010; 16: 3260-3269.
139. Barr PM, et al. Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant. Am J Hematol 2009; 8: 484-487.
140. Varterasian ML, et al. Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Clin Cancer Res 2000; 3: 825-828. (Pubitemid 30159336)
141. Winegarden JD, et al. A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer. Lung Cancer 2003; 2: 191-196. (Pubitemid 36173620)
142. Clamp AR, et al. A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma. Br J Cancer 2003; 7: 1152-1154. (Pubitemid 37363393)
143. Yap TA, et al. First-in-man phase I trial of two schedules of the novel synthetic tetrahydroisoquinoline alkaloid PM00104 (Zalypsis) in patients with advanced solid tumours. Br J Cancer 2012; 8: 1379-1385.
144. Massard C, et al. Phase I study of PM00104 (Zalypsis(R)) administered as a 1-hour weekly infusion resting every fourth week in patients with advanced solid tumors. Invest New Drugs 2013; 31: 623-630.
145. Potts BC, Lam KS,. Generating a generation of proteasome inhibitors: from microbial fermentation to total synthesis of salinosporamide a (marizomib) and other salinosporamides. Mar Drugs 2010; 4: 835-880.