Let’s make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment

Abstract

AbstractAdvancements in the CRISPR technology, a game-changer in experimental research, have revolutionized various fields of life sciences and more profoundly, cancer research. Cell death pathways are among the most deregulated in cancer cells and are considered as critical aspects in cancer development. Through decades, our knowledge of the mechanisms orchestrating programmed cellular death has increased substantially, attributed to the revolution of cutting-edge technologies. The heroic appearance of CRISPR systems have expanded the available screening platform and genome engineering toolbox to detect mutations and create precise genome edits. In that context, the precise ability of this system for identification and targeting of mutations in cell death signaling pathways that result in cancer development and therapy resistance is an auspicious choice to transform and accelerate the individualized cancer therapy. The concept of personalized cancer therapy stands on the identification of molecular characterization of the individual tumor and its microenvironment in order to provide a precise treatment with the highest possible outcome and minimum toxicity. This study explored the potential of CRISPR technology in precision cancer treatment by identifying and targeting specific cell death pathways. It showed the promise of CRISPR in finding key components and mutations involved in programmed cell death, making it a potential tool for targeted cancer therapy. However, this study also highlighted the challenges and limitations that need to be addressed in future research to fully realize the potential of CRISPR in cancer treatment. Graphical abstract Current application of CRISPR system in cancer therapy through a glance. A choosing the appropriate biological model for screening in vitro (using established cell lines, animal derived tumor cells, human derived tumor cells, stem cells or T cells), in vivo (using animal models which can harbor human derived tumor), or ex vivo (human/animal-derived organoids). B preparation of CRISPR gRNA library. C experimental design of CRISPR screening, identification of the desired gRNAs or phenotypic response. D CRISPR-Cas targeting of the identified targets, with Cas9 gene editing system (Knockout, base editing, prime editing), RNA modulation (modulation of RNA splicing, RNA base editing, RNA interference), and epigenomic edits and CRISPR interference/activation using dead Cas9 (dCas9) (Bock et al. 2022b)