Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism?
Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with peculiar functionalities that distinguish them from the bulk of tumor cells, most notably their tumor-initiating potential and drug resistance. Given these properties, it appears logical that CSCs have become an important tar...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-03-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00167/full |
| _version_ | 1811297455825747968 |
|---|---|
| author | Fabrizio Marcucci Carmelo Antonio Caserta Elisabetta Romeo Cristiano Rumio |
| author_facet | Fabrizio Marcucci Carmelo Antonio Caserta Elisabetta Romeo Cristiano Rumio |
| author_sort | Fabrizio Marcucci |
| collection | DOAJ |
| description | Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with peculiar functionalities that distinguish them from the bulk of tumor cells, most notably their tumor-initiating potential and drug resistance. Given these properties, it appears logical that CSCs have become an important target for many pharma companies. Antibody-drug conjugates (ADC) have emerged over the last decade as one of the most promising new tools for the selective ablation of tumor cells. Three ADCs have already received regulatory approval and many others are in different phases of clinical development. Not surprisingly, also a considerable number of anti-CSC ADCs have been described in the literature and some of these have entered clinical development. Several of these ADCs, however, have yielded disappointing results in clinical studies. This is similar to the results obtained with other anti-CSC drug candidates, including native antibodies, that have been investigated in the clinic. In this article we review the anti-CSC ADCs that have been described in the literature and, in the following, we discuss reasons that may underlie the failures in clinical trials that have been observed. Possible reasons relate to the biology of CSCs themselves, including their heterogeneity, the lack of strictly CSC-specific markers, and the capacity to interconvert between CSCs and non-CSCs; second, inherent limitations of some classes of cytotoxins that have been used for the construction of ADCs; third, the inadequacy of animal models in predicting efficacy in humans. We conclude suggesting some possibilities to address these limitations. |
| first_indexed | 2024-04-13T06:04:32Z |
| format | Article |
| id | doaj.art-ced2533a10094ddc881be68a5b78a07a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T06:04:32Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ced2533a10094ddc881be68a5b78a07a2022-12-22T02:59:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-03-01910.3389/fonc.2019.00167445531Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism?Fabrizio Marcucci0Carmelo Antonio Caserta1Elisabetta Romeo2Cristiano Rumio3Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyFondazione per la Medicina Solidale, Reggio Calabria, ItalyFondazione per la Medicina Solidale, Reggio Calabria, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyCancer stem-like cells (CSC) represent a subpopulation of tumor cells with peculiar functionalities that distinguish them from the bulk of tumor cells, most notably their tumor-initiating potential and drug resistance. Given these properties, it appears logical that CSCs have become an important target for many pharma companies. Antibody-drug conjugates (ADC) have emerged over the last decade as one of the most promising new tools for the selective ablation of tumor cells. Three ADCs have already received regulatory approval and many others are in different phases of clinical development. Not surprisingly, also a considerable number of anti-CSC ADCs have been described in the literature and some of these have entered clinical development. Several of these ADCs, however, have yielded disappointing results in clinical studies. This is similar to the results obtained with other anti-CSC drug candidates, including native antibodies, that have been investigated in the clinic. In this article we review the anti-CSC ADCs that have been described in the literature and, in the following, we discuss reasons that may underlie the failures in clinical trials that have been observed. Possible reasons relate to the biology of CSCs themselves, including their heterogeneity, the lack of strictly CSC-specific markers, and the capacity to interconvert between CSCs and non-CSCs; second, inherent limitations of some classes of cytotoxins that have been used for the construction of ADCs; third, the inadequacy of animal models in predicting efficacy in humans. We conclude suggesting some possibilities to address these limitations.https://www.frontiersin.org/article/10.3389/fonc.2019.00167/fullcancer stem cellepithelial-mesenchymal transitionresistanceantibody-drug conjugaterestingproliferating |
| spellingShingle | Fabrizio Marcucci Carmelo Antonio Caserta Elisabetta Romeo Cristiano Rumio Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism? Frontiers in Oncology cancer stem cell epithelial-mesenchymal transition resistance antibody-drug conjugate resting proliferating |
| title | Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism? |
| title_full | Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism? |
| title_fullStr | Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism? |
| title_full_unstemmed | Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism? |
| title_short | Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism? |
| title_sort | antibody drug conjugates adc against cancer stem like cells csc is there still room for optimism |
| topic | cancer stem cell epithelial-mesenchymal transition resistance antibody-drug conjugate resting proliferating |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00167/full |
| work_keys_str_mv | AT fabriziomarcucci antibodydrugconjugatesadcagainstcancerstemlikecellscscistherestillroomforoptimism AT carmeloantoniocaserta antibodydrugconjugatesadcagainstcancerstemlikecellscscistherestillroomforoptimism AT elisabettaromeo antibodydrugconjugatesadcagainstcancerstemlikecellscscistherestillroomforoptimism AT cristianorumio antibodydrugconjugatesadcagainstcancerstemlikecellscscistherestillroomforoptimism |