Antibody-Drug Conjugates (ADC) Against Cancer Stem-Like Cells (CSC)—Is There Still Room for Optimism?

Frontiers in Oncology

Cristiano Rumio¹  Fabrizio Marcucci¹  Elisabetta Romeo²  Carmelo Antonio Caserta² 

[1] Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy;Fondazione per la Medicina Solidale, Reggio Calabria, Italy;

关键词: cancer stem cell;    epithelial-mesenchymal transition;    resistance;    antibody-drug conjugate;    resting;    proliferating;   

DOI  :  10.3389/fonc.2019.00167

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown