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Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy
We review drug conjugates combining a tumor-selective moiety with a cytotoxic agent as cancer treatments. Currently, antibody-drug conjugates (ADCs) are the most common drug conjugates used clinically as cancer treatments. While providing both efficacy and favorable tolerability, ADCs have limitatio...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512983/ https://www.ncbi.nlm.nih.gov/pubmed/34641586 http://dx.doi.org/10.3390/molecules26196042 |
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author | Lindberg, Jakob Nilvebrant, Johan Nygren, Per-Åke Lehmann, Fredrik |
author_facet | Lindberg, Jakob Nilvebrant, Johan Nygren, Per-Åke Lehmann, Fredrik |
author_sort | Lindberg, Jakob |
collection | PubMed |
description | We review drug conjugates combining a tumor-selective moiety with a cytotoxic agent as cancer treatments. Currently, antibody-drug conjugates (ADCs) are the most common drug conjugates used clinically as cancer treatments. While providing both efficacy and favorable tolerability, ADCs have limitations due to their size and complexity. Peptides as tumor-targeting carriers in peptide-drug conjugates (PDCs) offer a number of benefits. Melphalan flufenamide (melflufen) is a highly lipophilic PDC that takes a novel approach by utilizing increased aminopeptidase activity to selectively increase the release and concentration of cytotoxic alkylating agents inside tumor cells. The only other PDC approved currently for clinical use is (177)Lu-dotatate, a targeted form of radiotherapy combining a somatostatin analog with a radionuclide. It is approved as a treatment for gastroenteropancreatic neuroendocrine tumors. Results with other PDCs combining synthetic analogs of natural peptide ligands with cytotoxic agents have been mixed. The field of drug conjugates as drug delivery systems for the treatment of cancer continues to advance with the application of new technologies. Melflufen provides a paradigm for rational PDC design, with a targeted mechanism of action and the potential for deepening responses to treatment, maintaining remissions, and eradicating therapy-resistant stem cells. |
format | Online Article Text |
id | pubmed-8512983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85129832021-10-14 Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy Lindberg, Jakob Nilvebrant, Johan Nygren, Per-Åke Lehmann, Fredrik Molecules Review We review drug conjugates combining a tumor-selective moiety with a cytotoxic agent as cancer treatments. Currently, antibody-drug conjugates (ADCs) are the most common drug conjugates used clinically as cancer treatments. While providing both efficacy and favorable tolerability, ADCs have limitations due to their size and complexity. Peptides as tumor-targeting carriers in peptide-drug conjugates (PDCs) offer a number of benefits. Melphalan flufenamide (melflufen) is a highly lipophilic PDC that takes a novel approach by utilizing increased aminopeptidase activity to selectively increase the release and concentration of cytotoxic alkylating agents inside tumor cells. The only other PDC approved currently for clinical use is (177)Lu-dotatate, a targeted form of radiotherapy combining a somatostatin analog with a radionuclide. It is approved as a treatment for gastroenteropancreatic neuroendocrine tumors. Results with other PDCs combining synthetic analogs of natural peptide ligands with cytotoxic agents have been mixed. The field of drug conjugates as drug delivery systems for the treatment of cancer continues to advance with the application of new technologies. Melflufen provides a paradigm for rational PDC design, with a targeted mechanism of action and the potential for deepening responses to treatment, maintaining remissions, and eradicating therapy-resistant stem cells. MDPI 2021-10-05 /pmc/articles/PMC8512983/ /pubmed/34641586 http://dx.doi.org/10.3390/molecules26196042 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Lindberg, Jakob Nilvebrant, Johan Nygren, Per-Åke Lehmann, Fredrik Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy |
title | Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy |
title_full | Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy |
title_fullStr | Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy |
title_full_unstemmed | Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy |
title_short | Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy |
title_sort | progress and future directions with peptide-drug conjugates for targeted cancer therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512983/ https://www.ncbi.nlm.nih.gov/pubmed/34641586 http://dx.doi.org/10.3390/molecules26196042 |
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