Peptide-platinum(IV) conjugation minimizes the negative impact of current anticancer chemotherapy on nonmalignant cells
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- dc.contributor.author Linares Aceituno, Jenniffer Lissethe
- dc.contributor.author Varese, Monica
- dc.contributor.author Sallent-Aragay, Anna
- dc.contributor.author Méndez, Ana
- dc.contributor.author Palomo-Ponce, Sergio
- dc.contributor.author Iglesias Coma, Mar
- dc.contributor.author Batlle Gómez, Eduard
- dc.contributor.author Pisonero, Jorge
- dc.contributor.author Montagut Viladot, Clara
- dc.contributor.author Giralt, Ernest
- dc.contributor.author Lo Re, Daniele
- dc.contributor.author Calon, Alexandre
- dc.date.accessioned 2024-02-13T14:37:51Z
- dc.date.issued 2023
- dc.description.abstract The relative success of platinum (Pt)-based chemotherapy comes at the cost of severe adverse side effects and is associated with a high risk of pro-oncogenic activation in the tumor microenvironment. Here, we report the synthesis of C-POC, a novel Pt(IV) cell-penetrating peptide conjugate showing a reduced impact against nonmalignant cells. In vitro and in vivo evaluation using patient-derived tumor organoids and laser ablation inductively coupled plasma mass spectrometry indicates that C-POC maintains robust anticancer efficacy while displaying diminished accumulation in healthy organs and reduced adverse toxicity compared to the standard Pt-based therapy. Likewise, C-POC uptake is significantly lowered in the noncancerous cells populating the tumor microenvironment. This results in the downregulation of versican, a biomarker of metastatic spreading and chemoresistance that we found upregulated in patients treated with standard Pt-based therapy. Altogether, our findings underscore the importance of considering the off-target impact of anticancer treatment on normal cells to improve drug development and patient care.
- dc.format.mimetype application/pdf
- dc.identifier.citation Linares J, Varese M, Sallent-Aragay A, Méndez A, Palomo-Ponce S, Iglesias M, Batlle E, Pisonero J, Montagut C, Giralt E, Lo Re D, Calon A. Peptide-platinum(IV) conjugation minimizes the negative impact of current anticancer chemotherapy on nonmalignant cells. J Med Chem. 2023 Mar 9;66(5):3348-55. DOI: 10.1021/acs.jmedchem.2c01717
- dc.identifier.doi http://dx.doi.org/10.1021/acs.jmedchem.2c01717
- dc.identifier.issn 0022-2623
- dc.identifier.uri http://hdl.handle.net/10230/59102
- dc.language.iso eng
- dc.publisher American Chemical Society (ACS)
- dc.relation.ispartof J Med Chem. 2023 Mar 9;66(5):3348-55
- dc.rights This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of medicinal chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.jmedchem.2c01717.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Quimioteràpia
- dc.title Peptide-platinum(IV) conjugation minimizes the negative impact of current anticancer chemotherapy on nonmalignant cells
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion