Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63.

Article  PubMed  Google Scholar 

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48.

Article  PubMed  Google Scholar 

Liu B, Zhou H, Tan L, Siu KTH, Guan XY. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduction Targeted Therapy. 2024;9:1–44. Available from: https://www.nature.com/articles/s41392-024-01856-7

Mishra R, Kumar N, Sachan N. Synthesis, pharmacological evaluation, and in-silico studies of thiophene derivatives. Oncologie. 2021;23.

Püsküllüoğlu M, Michalak I. An ocean of possibilities: a review of marine organisms as sources of nanoparticles for cancer care. Nanomedicine (Lond). 2022;17:1695–719. Available from: https://pubmed.ncbi.nlm.nih.gov/36562416/

Beeton C. Chapter 64—Targets and therapeutic properties. In: Kastin AJ, editor. Handbook of biologically active peptides. 2nd ed. Boston: Academic press; 2013. p. 473–82.

Chapter  Google Scholar 

Chun HG, Davies B, Hoth D, Suffness M, Plowman J, Flora K, et al. Didemnin B. The first marine compound entering clinical trials as an antineoplastic agent. Invest New Drugs. 1986;4:279–84. Available from: https://pubmed.ncbi.nlm.nih.gov/3546184/

Ma L, Zhang Q, Yang C, Zhu Y, Zhang L, Wang L, et al. Assembly line and post-PKS modifications in the biosynthesis of marine polyketide natural products. Compr Nat Products. 2019;III:139–97.

Google Scholar 

Lee J, Currano JN, Carroll PJ, Joullié MM. Didemnins, tamandarins and related natural products. Nat Prod Rep. 2012;29:404–24. Available from: https://pubs.rsc.org/en/content/articlehtml/2012/np/c2np00065b

Potts MB, McMillan EA, Rosales TI, Kim HS, Ou YH, Toombs JE, et al. Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B. Nat Chem Biol. 2015;11:401–8. Available from: https://pubmed.ncbi.nlm.nih.gov/25867045/

Stankey RJ, Johnson D, Duggan BM, Mead DA, La Clair JJ. A survey of Didemnin Depsipeptide production in Tistrella. Mar Drugs. 2023;21:56. Available from: https://pubmed.ncbi.nlm.nih.gov/36827097/

Rinehart KL, Gloer JB, Hughes RG, Renis HE, Patrick McGovren J, Swynenberg EB, et al. Didemnins: antiviral and antitumor depsipeptides from a caribbean tunicate. Science. 1981;212:933–5. Available from: https://pubmed.ncbi.nlm.nih.gov/7233187/

Ramesh C, Tulasi BR, Raju M, Thakur N, Dufossé L. Marine natural products from tunicates and their associated microbes. Mar Drugs. 2021;19:308. Available from: https://pubmed.ncbi.nlm.nih.gov/34073515/

Mishra R, Kumar N, Mishra I, Sachan N. A review on anticancer activities of Thiophene and its analogs. Mini Rev Med Chem. 2020;20:1944–65. Available from: https://pubmed.ncbi.nlm.nih.gov/32669077/

Tsukimoto M, Nagaoka M, Shishido Y, Fujimoto J, Nishisaka F, Matsumoto S, et al. Bacterial production of the tunicate-derived antitumor cyclic depsipeptide didemnin B. J Nat Prod. 2011;74:2329–31. Available from: https://pubmed.ncbi.nlm.nih.gov/22035372/

Sakai R, Stroh JG, Sullins DW, Rinehart KL. Seven new Didemnins from the marine Tunicate Trididemnum solidum. J Am Chem Soc. 1995;117:3734–48. Available from: https://pubs.acs.org/doi/abs/10.1021/ja00118a010

Maharani R, Sleebs BE, Hughes AB. Macrocyclic N-methylated cyclic peptides and depsipeptides. Stud Nat Prod Chem. 2015;44:113–249.

Article  Google Scholar 

Rinehart KL. Antitumor compounds from tunicates. Med Res Rev. 2000;1–27.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2023 update. Nucleic Acids Res. 2023;51:D1373–80. Available from: https://pubmed.ncbi.nlm.nih.gov/36305812/

Didemnin A | C49H78N6O12 | CID 123844 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Didemnin-A#section=2D-Structure

Didemnin B | C57H89N7O15 | CID 122651 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Didemnin-B#section=2D-Structure

Didemnin C | C52H82N6O14 | CID 9963211 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Didemnin-C#section=2D-Structure

Didemnin X | C82H130N12O24 | CID 44592545 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/didemnin-X#section=2D-Structure

Didemnin Y | C87H138N14O26 | CID 44592546 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/44592546#section=2D-Structure

Trabectedin | C39H43N3O11S | CID 108150 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Trabectedin#section=2D-Structure

Plitidepsin | C57H87N7O15 | CID 9812534 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Plitidepsin#section=2D-Structure

Bryostatin | C47H68O17 | CID 6435419 - PubChem [Internet]. [cited 2024 Dec 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Bryostatin#section=2D-Structure

Thell K, Hellinger R, Schabbauer G, Gruber CW. Immunosuppressive peptides and their therapeutic applications. Drug Discov Today. 2014;19:645–53. Available from: /pmc/articles/PMC4042018/

Kang HK, Choi MC, Seo CH, Park Y. Therapeutic properties and biological benefits of marine-derived anticancer peptides. Int J Mol Sci. 2018;19:919. Available from: /pmc/articles/PMC5877780/

Schmidt U, Griesser H, Haas G, Kroner M, Riedl B, Schumacher A, et al. Synthesis and cytostatic activities of didemnin derivatives*. J Peptide Res. 1999;54:146–61. Available from: https://onlinelibrary.wiley.com/doi/full/10.1034/j.1399-3011.1999.00097.x

Rinehart K, Kishore V, Bible K, Sakai R, Sullins D, Li K. Didemnins and Tunichlorin: Novel natural products from the Marine Tunicate Trididemnum solidum. J Nat Prod. 1988;51:624. Available from: https://pubmed.ncbi.nlm.nih.gov/21401178/

Nuzzo G, Senese G, Gallo C, Albiani F, Romano L, D’ippolito G, et al. Antitumor potential of immunomodulatory natural products. Mar Drugs. 2022;20:386. Available from: /pmc/articles/PMC9229642/

Cuevas C, Francesch A. Development of Yondelis (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat Prod Rep. 2009;26:322–37. Available from: https://pubmed.ncbi.nlm.nih.gov/19240944/

Ahmed S, Mirzaei H, Aschner M, Khan A, Al-Harrasi A, Khan H. Marine peptides in breast cancer: therapeutic and mechanistic understanding. Biomed Pharmacother. 2021;142:112038. Available from: https://pubmed.ncbi.nlm.nih.gov/34411915/

Benvenuto JA, Newman RA, Bignami GS, Raybould TJG, Raber MN, Esparza L, et al. Phase II clinical and pharmacological study of didemnin B in patients with metastatic breast cancer. Invest New Drugs. 1992;10:113–7. Available from: https://pubmed.ncbi.nlm.nih.gov/1500265/

Beasley VR, Bruno SJ, Burner JS, Choi BW, Rinehart KL, Koritz GD, et al. Fate of tritiated didemnin B in mice: excretion and tissue concentrations after an intraperitoneal dose. Biopharm Drug Dispos. 2005;26:341–51. Available from: https://pubmed.ncbi.nlm.nih.gov/16082719/

Andrew Dorr F, Kuhn JG, Phillips J, von Hoff DD. Phase I clinical and pharmacokinetic investigation of didemnin B, a cyclic depsipeptide. Eur J Cancer Clin Oncol. 1988;24:1699–706.

Article  Google Scholar 

Amador ML, Jimeno J, Paz-Ares L, Cortes-Funes H, Hidalgo M. Progress in the development and acquisition of anticancer agents from marine sources. Ann Oncol. 2003;14:1607–15.

Article  CAS  PubMed  Google Scholar 

Stewart JA, Low JB, Roberts JD, Blow A. A phase I clinical trial of didemnin B. Cancer. 1991;68:2550–4.

Article  CAS  PubMed  Google Scholar 

Ahuja D, Vera MD, SirDeshpande B V., Morimoto H, Williams PG, Joullié MM, et al. Inhibition of protein synthesis by didemnin B: how EF-1alpha mediates inhibition of translocation. Biochemistry. 2000;39:4339–46. Available from: https://pubmed.ncbi.nlm.nih.gov/10757982/

Mayer AMS, Gustafson KR. Marine pharmacology in 2000: antitumor and cytotoxic compounds. Int J Cancer. 2003;105:291–9. Available from: https://pubmed.ncbi.nlm.nih.gov/12704660/

Jiang TL, Liu RH, Salmon SE. Antitumor activity of didemnin B in the human tumor stem cell assay. Cancer Chemother Pharmacol. 1983;11:1–4. Available from: https://pubmed.ncbi.nlm.nih.gov/6883622/

Crampton SL, Adams EG, Kuentzel SL, Li LH, Badiner G, Bhuyan1 BK. Biochemical and cellular effects of Didemnins A and B. Cancer Res. 1984;44:1796–801. Available from: http://aacrjournals.org/cancerres/article-pdf/44/5/1796/2418747/cr0440051796.pdf

Dalisay DS, Tenebro CP, Sabido EM, Suarez AFL, Paderog MJV, Reyes-Salarda R, et al. Marine-derived anticancer agents targeting apoptotic pathways: exploring the depths for novel cancer therapies. Mar Drugs. 2024;22. https://doi.org/10.3390/md22030114. Available from: https://pubmed.ncbi.nlm.nih.gov/38535455/

Yap SQ, Mathavarajah S, Huber RJ. The converging roles of Batten disease proteins in neurodegeneration and cancer. iScience. 2021;24:102337. Available from: https://pubmed.ncbi.nlm.nih.gov/33889828/

Stoneley M, Harvey RF, Mulroney TE, Mordue R, Jukes-Jones R, Cain K, et al. Unresolved stalled ribosome complexes restrict cell-cycle progression after genotoxic stress. Mol Cell. 2022;82:1557. Available from: /pmc/articles/PMC9098122/

Erba E, Bassano L, Di Liberti G, Muradore I, Chiorino G, Ubezio P, et al. Cell cycle phase perturbations and apoptosis in tumour cells induced by aplidine. Br J Cancer. 2002;86:1510–7. Available from: https://pubmed.ncbi.nlm.nih.gov/11986788/

Dayanidhi DL, Thomas BC, Osterberg JS, Vuong M, Vargas G, Kwartler SK, et al. Exploring the diversity of the marine environment for new anti-cancer compounds. Front Mar Sci. 2021;7:614766. Available from: www.frontiersin.org

Tong M, Jiang Y. FK506-binding proteins and their diverse functions. Curr Mol Pharmacol. 2015;9:48–65. Available from: https://pubmed.ncbi.nlm.nih.gov/25986568/

Kamali AN, Bautista JM, Eisenhut M, Hamedifar H. Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands. Ther Adv Vaccines Immunother. 2023;11:25151355231192044. Available from: /pmc/articles/PMC10469281/

Shin DM, Holoye PY, Murphy WK, Forman A, Papasozomenos SC. Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting. Cancer Chemother Pharmacol. 1991;29:145–9. Available from: https://link.springer.com/article/10.1007/BF00687325

Jones D V., Ajani JA, Blackburn R, Daugherty K, Levin B, Patt YZ, et al. Phase II study of didemnin B in advanced colorectal cancer. Invest New Drugs. 1992;10:211–3. Available from: https://pubmed.ncbi.nlm.nih.gov/1428730/

Search for: aplidin | ClinicalTrials.gov [Internet]. [cited 2024 Sep 2]. Available from: https://clinicaltrials.gov/search?intr=aplidin

Faivre S, Chièze S, Delbaldo C, Ady-Vago N, Guzman C, Lopez-Lazaro L, et al. Phase I and pharmacokinetic study of aplidine, a new marine cyclodepsipeptide in patients with advanced malignancies. 2016;23:7871–80. Available from: https://ascopubs.org/doi/10.1200/JCO.2005.09.357

Geoerger B, Estlin EJ, Aerts I, Kearns P, Gibson B, Corradini N, et al. A phase I and pharmacokinetic study of plitidepsin in children with advanced solid tumours: an Innovative Therapies for Children with Cancer (ITCC) study. Eur J Cancer. 2012;48:289–96. Available from: https://pubmed.ncbi.nlm.nih.gov/22119199/

Toulmonde M, Le Cesne A, Piperno-Neumann S, Penel N, Chevreau C, Duffaud F, et al. Aplidin in patients with advanced dedifferentiated liposarcomas: a French Sarcoma Group Single-Arm Phase II study. Ann Oncol. 2015;26:1465–70. Available from: https://pubmed.ncbi.nlm.nih.gov/26041763/

Schöffski P, Guillem V, Garcia M, Rivera F, Tabernero J, Cullell M, et al. Phase II randomized study of Plitidepsin (Aplidin), alone or in association with L-carnitine, in patients with unresectable advanced renal cell carcinoma. Mar Drugs. 2009;7:57–70. Available from: https://pubmed.ncbi.nlm.nih.gov/19370171/

Peschel C, Hartmann JT, Schmittel A, Bokemeyer C, Schneller F, Keilholz U, et al. Phase II study of plitidepsin in pretreated patients with locally advanced or metastatic non-small cell lung cancer. Lung Cancer. 2008;60:374–80. Available from: https://pubmed.ncbi.nlm.nih.gov/18054408/

Dumez H, Gallardo E, Culine S, Galceran JC, Schöffski P, Droz JP, 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;7:451–63. Available from: https://pubmed.ncbi.nlm.nih.gov/19841725/

Spicka I, Ocio EM, Oakervee HE, Greil R, Banh RH, Huang SY, et al. Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma. Ann Hematol. 2019;98:2139–50. Available from: https://pubmed.ncbi.nlm.nih.gov/31240472/

Ribrag V, Caballero D, Fermé C, Zucca E, Arranz R, Briones J, et al. Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin’s lymphoma. Haematologica. 2013;98:357–63. Available from: https://pubmed.ncbi.nlm.nih.gov/23065525/

Aspeslagh S, Awada A, Matos-Pita AS, Aftimos P, Bahleda R, Varga A, et al. Phase I dose-escalation study of plitidepsin in combination with bevacizumab in patients with refractory solid tumors. Anticancer Drugs. 2016;27:1021–7. Available from: https://pubmed.ncbi.nlm.nih.gov/27610894/

Salazar R, Plummer R, Oaknin A, Robinson A, Pardo B, Soto-Matos A, et al. Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin in patients with advanced solid tumors or lymphomas. Invest New Drugs. 2011;29:1406–13. Available from: https://pubmed.ncbi.nlm.nih.gov/20623160/

Dou X, Dong B. Origins and bioactivities of natural compounds derived from marine ascidians and their symbionts. Mar Drugs. 2019;17:670. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6950356/

Weiss RB, Peterson BL, Allen SL, Browning SM, Duggan DB, Schiffer CA. A phase II trial of didemnin B in myeloma. A Cancer and Leukemia Group B (CALGB) study. Invest New Drugs. 1994;12:41–3. Available from: https://pubmed.ncbi.nlm.nih.gov/7960604/

Capalbo A, Lauritano C. Multiple myeloma: possible cure from the sea. Cancers. 2022;14:2965. Available from: https://www.mdpi.com/2072-6694/14/12/2965/htm

Cain JM, Liu PY, Alberts DE, Gallion HH, Laufman L, O’Sullivan J, et al. Phase II trial of didemnin-B in advanced epithelial ovarian cancer. A Southwest Oncology Group study. Invest New Drugs. 1992;10:23–4. Available from: https://pubmed.ncbi.nlm.nih.gov/1607250/

Williamson SK, Wolf MK, Eisenberger MA, O’Rourke M, Brannon W, Crawford ED. Phase II evaluation of didemnin B in hormonally refractory metastatic prostate cancer. A Southwest Oncology Group study. Invest New Drugs. 1995;13:167–70. Available from: https://pubmed.ncbi.nlm.nih.gov/8617581/

Hochster H, Oratz R, Ettinger DS, Borden E. A phase II study of Didemnin B (NSC 325319) in advanced malignant melanoma: an eastern cooperative oncology group study (PB687). Invest New Drugs. 1998;16:259–63.

Article  CAS  PubMed  Google Scholar 

Van Kesteren C, De Vooght MMM, López-Lázaro L, Mathôt RAA, Schellens JHM, Jimeno JM, et al. Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine origin. Anticancer Drugs. 2003;14:487–502. Available from: https://pubmed.ncbi.nlm.nih.gov/12960733/

Larsen AK, Galmarini CM, D’Incalci M. Unique features of trabectedin mechanism of action. Cancer Chemother Pharmacol. 2016;77:663–71. Available from: https://pubmed.ncbi.nlm.nih.gov/26666647/

Raghuvanshi R, Bharate SB. Preclinical and clinical studies on Bryostatins, a class of marine-derived protein kinase C modulators: a mini-review. Curr Top Med Chem. 2020;20:1124–35. Available from: https://benthamscience.com/article/105477

Tran UP, Billingsley KL. Biological evaluation of indolactams for in vitro bryostatin 1-like activity. Bioorg Med Chem Lett. 2024;97:129570. Available from: https://pubmed.ncbi.nlm.nih.gov/38036273/

Lee HS, Jeong GS. Salinosporamide A, a marine-derived proteasome inhibitor, inhibits T cell activation through regulating proliferation and the cell cycle. Molecules. 2020;25:5031. Available from: /pmc/articles/PMC7663257/

Boccia SM, Sassu CM, Ergasti R, Vertechy L, Apostol AI, Palluzzi E, et al. Focus on trabectedin in ovarian cancer: what do we still need to know? Drug Des Devel Ther. 2024;18:2021–32. Available from: https://pubmed.ncbi.nlm.nih.gov/38863768/

Fisher JF, Mobashery S. β-Lactams from the Ocean. Mar Drugs. 2023;21. Available from: https://pubmed.ncbi.nlm.nih.gov/36827127/

Michalak I, Püsküllüoğlu M. Look into my onco-forest—review of plant natural products with anticancer activity. Curr Top Med Chem. 2022;22:922–38. Available from: http://www.ncbi.nlm.nih.gov/pubmed/35240958

Stankey RJ, Johnson D, Duggan BM, Mead DA, La Clair JJ. A survey of Didemnin Depsipeptide production in Tistrella. Mar Drugs. 2023;21. Available from: https://pubmed.ncbi.nlm.nih.gov/36827097/

Zou X, Hui Z, Shepherd RA, Zhao S, Wu Y, Shen Z, et al. Unveiling a CAAX protease-like protein involved in Didemnin drug maturation and secretion. Adv Sci (Weinh). 2024;11. Available from: https://pubmed.ncbi.nlm.nih.gov/38032137/

Xu Y, Kersten RD, Nam SJ, Lu L, Al-Suwailem AM, Zheng H, et al. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents. J Am Chem Soc. 2012;134:8625–32. Available from: https://pubmed.ncbi.nlm.nih.gov/22458477/

Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget. 2017;8:38022–43. Available from: https://pubmed.ncbi.nlm.nih.gov/28410237/

Zhang H, Li X, Hui Z, Huang S, Cai M, Shi W, et al. A semisynthesis platform for the efficient production and exploration of didemnin-based drugs. Angew Chem Int Ed Engl. 2024;63. Available from: https://pubmed.ncbi.nlm.nih.gov/38291557/