In plants, resistance genes (R) are key players in combatting diseases caused by various phytopathogens. Typically, resistance relies on detecting a single pathogen-derived molecular pattern. However, R-gene-mediated resistance is often race specific, follows the gene-for-gene hypothesis, and can be overcome in field conditions as pathogens evolve. On the contrary, altering plant susceptibility genes (S-genes) facilitates compatibility and results in broad and durable resistance. S-genes are negative regulators present in plants and exploited by pathogens to facilitate their growth and cause infection. Several studies across crop species have reported manipulation of S-genes using genome editing to confer broad spectrum resistance. This review focuses on the plant defense mechanism against biotic stress, R-genes vs. S-genes, different types/classes of S-genes, different tools for S-gene discovery, and the use of gene editing technologies to target S-genes in addition to their applications, challenges, and future perspectives.

Cucumber (Cucumis sativus L.) is a globally important crop valued for both fresh consumption and processing, particularly in the United States. It was the first specialty crop among horticultural crops with a publicly available draft genome, providing a foundation for molecular breeding and trait discovery. However, cucumber production faces significant yield losses due to a wide range of biotic stresses. The crop is highly susceptible to fungal, viral, and bacterial pathogens throughout its lifecycle. To combat these challenges, breeders deploy conventional and contemporary breeding strategies to develop disease-resistant cultivars. Advances in high-throughput sequencing and genomic tools, such as quantitative trait loci mapping, genome-wide association studies, and genomic selection, have accelerated the identification and subsequent integration of resistance genes and loci into elite cucumber germplasm. This review highlights recent progress in resistance breeding for biotic stress management in cucumber, with a focus on major diseases caused by fungal, viral, and bacterial pathogens. It emphasizes the role of genomic tools, the discovery of key resistance genes and QTLs, and the potential of modern breeding approaches to improve crop resilience. Continued innovation and integration of emerging technologies will be essential for developing durable, broad-spectrum resistance in future cucumber cultivars.