Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104)
- PMID: 23588839
- DOI: 10.1002/ijc.28213
Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104)
Abstract
This study: (i) investigated the in vitro cytotoxicity and mode of action of lurbinectedin (PM01183) and Zalypsis® (PM00104) compared with trabectedin in cell lines deficient in specific mechanisms of repair, (ii) evaluated their in vivo antitumor activity against a series of murine tumors and human xenografts. The antiproliferative activity, the DNA damage and the cell cycle perturbations induced by the three compounds on tumor lines were very similar. Nucleotide Excision Repair (NER) deficient cells were approximately fourfold more resistant to trabectedin, lurbinectedin and Zalypsis®. Cells deficient in non-homologous end joining (NHEJ), MRN complex and translesion synthesis (TLS) were slightly more sensitive to the three compounds (approximately fivefold) while cells deficient in homologous recombination (HR) were markedly more sensitive (150-200-fold). All three compounds showed a good antitumor activity in several in vivo models. Lurbinectedin and trabectedin had a similar pattern of antitumor activity in murine tumors and in xenografts, whereas Zalypsis® appeared to have a distinct spectrum of activity. The fact that no relationship whatsoever was found between the in vitro cytotoxic potency and the in vivo antitumor activity, suggests that in addition to direct cytotoxic mechanisms other host-mediated effects are involved in the in vivo pharmacological effects.
Keywords: DNA damage and repair mechanisms; Zalypsis®; animal models of cancers; cellular response to anticancer drugs; control of cell cycle progression; lurbinectedin; novel marine antitumor agents; trabectedin.
© 2013 UICC.
Similar articles
-
Trabectedin and its C subunit modified analogue PM01183 attenuate nucleotide excision repair and show activity toward platinum-resistant cells.Mol Cancer Ther. 2011 Aug;10(8):1481-9. doi: 10.1158/1535-7163.MCT-11-0252. Epub 2011 May 27. Mol Cancer Ther. 2011. PMID: 21622731
-
Ascites interferes with the activity of lurbinectedin and trabectedin: Potential role of their binding to alpha 1-acid glycoprotein.Biochem Pharmacol. 2017 Nov 15;144:52-62. doi: 10.1016/j.bcp.2017.08.001. Epub 2017 Aug 4. Biochem Pharmacol. 2017. PMID: 28782526
-
Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair.Oncotarget. 2016 May 3;7(18):25885-901. doi: 10.18632/oncotarget.8292. Oncotarget. 2016. PMID: 27029031 Free PMC article.
-
Trabectedin mechanism of action: what's new?Future Oncol. 2013 Dec;9(12 Suppl):5-10. doi: 10.2217/fon.13.207. Future Oncol. 2013. PMID: 24195524 Review.
-
Unique features of trabectedin mechanism of action.Cancer Chemother Pharmacol. 2016 Apr;77(4):663-71. doi: 10.1007/s00280-015-2918-1. Epub 2015 Dec 14. Cancer Chemother Pharmacol. 2016. PMID: 26666647 Review.
Cited by
-
Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy.J Clin Oncol. 2018 Nov 1;36(31):3134-3143. doi: 10.1200/JCO.2018.78.6558. Epub 2018 Sep 21. J Clin Oncol. 2018. PMID: 30240327 Free PMC article. Clinical Trial.
-
Synergistic Effect of Trabectedin and Olaparib Combination Regimen in Breast Cancer Cell Lines.J Breast Cancer. 2015 Dec;18(4):329-38. doi: 10.4048/jbc.2015.18.4.329. Epub 2015 Dec 23. J Breast Cancer. 2015. PMID: 26770239 Free PMC article.
-
Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Mol Cancer Ther. 2025 Jun 4;24(6):828-839. doi: 10.1158/1535-7163.MCT-24-0050. Mol Cancer Ther. 2025. PMID: 39636909 Free PMC article. Review.
-
Effects of the Anti-Tumor Agents Trabectedin and Lurbinectedin on Immune Cells of the Tumor Microenvironment.Front Oncol. 2022 Mar 1;12:851790. doi: 10.3389/fonc.2022.851790. eCollection 2022. Front Oncol. 2022. PMID: 35299737 Free PMC article. Review.
-
Anti-cancer effect and gene modulation of ET-743 in human biliary tract carcinoma preclinical models.BMC Cancer. 2014 Dec 5;14:918. doi: 10.1186/1471-2407-14-918. BMC Cancer. 2014. PMID: 25479910 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials