In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues

Méry, Benoite; Guy, Jean-Baptiste; Vallard, Alexis; Espenel, Sophie; Ardail, Dominique; Rodriguez-Lafrasse, Claire; Rancoule, Chloé; Magné, Nicolas

A better understanding of cell death mechanisms is a sine qua non condition for improving the process of drug discovery. In a recent review, Rello-Varona et al 51 claim that the correct evaluation of cell death in every experimental setting related to cancer research is a must and advocate for a real cell death characterization so as to understand therapeutic failure, treatment-related side effects, and even provide susceptibility markers. Furthermore, this crucial assessment leads to chemotherapeutic approaches for targeting specific cell death pathways, and several novel drugs are being currently tested in 6 Journal of Cell Death clinic, mostly in phase I and II trials. To develop new drug combinations, a further understanding of the accurate effect of chemotherapy on the death signaling pathways is still required. 52 Cell death remains a central basis in every therapeutic approach regarding cancer. Recently, in the specific field of antisarcoma therapy, the assessment of cell death mechanisms has been published, and the authors highlight the fact that sarcoma research needs the implementation of a better determination of cell death mechanisms to understand chemoresistance and cell death immunogenic potential. Several clinical trials that evaluate target therapies in sarcomas regarding apoptosis and mitotic catastrophe are still ongoing. 53 Concerning the innovative concept of immunogenic cell death, the induction of this form of death through nanocarrier-based drug delivery systems may lead to potential therapy in pancreatic cancer, hence the need to possess strong cell death assays to explore the potential role of immunogenic cell death in nanomedicines. 54