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Antibody-drug Conjugates Against Cancer Stem-Like Cells: The Current State of The Art.

Published on 26th February

Cancer-stem like cells, also known as CSC, possess the capacity for self-renewal and may cause the heterogeneous lineages of cancer cells that comprise the tumor. They represent a subpopulation of tumor cells and distinguish themselves from the bulk of tumor cells by their tumor-initiating potential and drug resistance. Given these properties, CSCs have become an important target for many drug developers. [1]

Antibody-drug conjugates or ADCs have emerged as one of the most promising tools for the selective ablation of tumor cells. To date, four ADCs have received regulatory approval. In addition. a large number of investigational ADCs are in different phases of clinical development.

A considerable number of anti-CSC ADCs have been described in the literature. Some of these investigational agents have entered clinical development. Several of these ADCs, however, have yielded disappointing results. This is similar to the results obtained other anti-CSC drug candidates, including native antibodies.

In new article published in Frontiers in Oncology, Fabrizio Marcucci at the Department of Pharmacological and Biomolecular Sciences, Department of Pharmacological and Biomolecular Sciences, Faculty of Pharmacy, University of Milan, Italy, and Elisabetta L. Romeo, Carmelo A. Caserta and Cristiano Rumio from the University of Milan, Italy review the anti-CSC ADCs that have been described in the literature.

The authors 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.

They also discuss the inherent limitations of some classes of cytotoxins that have been used for the construction of ADCs and, finally, they discuss the inadequacy of animal models in predicting efficacy in humans.

The authors conclude their review by suggesting some possibilities to address these limitations.

Marcucci F, Romeo EL, Caserta CA, Rumio C. Antibody-drug Conjugates (ADC) Against Cancer Stem-Like Cell (CSC) – Is There Still Room for Optimism? Front. Oncol. | doi: 10.3389/fonc.2019.00167 [Article]

Last Editorial Review: February 26, 2019

Featured Image: Research Courtesy: © 2019 Fotolia. Used with permission.

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