Synthetic lethality in cancer: a protocol for scoping review of gene interactions from synthetic lethal screens and functional studies.

Background: Two genes are synthetically lethal if loss of function of either one of the two genes does not result in cell death, whereas loss of function of both genes together results in being detrimental to cell survival. This concept has been the basis for developing personalized, precision treatments, which can selectively damage tumor cells and minimize toxicity to normal tissues. Tumor cells often harbor mutations in genes involved in DNA repair pathways, forcing them to switch to alternative repair pathways, leading to chemotherapeutic resistance. These interactions, if targeted, could be synthetically lethal. We aimed to summarize synthetically lethal gene pairs that could be utilized to selectively target cancer cells and minimize side effects on normal tissues. The objective of this review is to study druggable synthetically lethal gene pairs for targeted cancer therapy that have been identified through various genetic screens and functional studies.

Methods: A systematic literature search will be conducted to extract synthetically lethal gene pairs that can be specifically targeted to cancer cells. Owing to the relatively recent research pertaining to this field, the literature search will incorporate data from 1956. The search will be conducted on PubMed, Web of Science, Embase, and Scopus. The narrative approach will guide the analysis and synthesis of the results.

Discussion: This review highlights scientific articles that report druggable synthetically lethal gene pairs by testing the efficacy of targeted inhibitors in clonogenic assays. These include research studies that identify synthetically lethal gene pairs detected through CRISPR screens by knocking out one or two genes within the same cell and testing the potency of inhibitors to specifically kill malignant cells.

Systematic review registration: https://doi.org/10.17605/OSF.IO/5BCW6 .