Advances in Functional Genomics of Disease Resistance in Cucumber (Cucumis sativus) and Translational Prospects for the Cucurbitaceae Family

Cucurbit crops—including cucumber (Cucumis sativus), watermelon (Citrullus lanatus), and melon (Cucumis melo)—are of major economic and nutritional importance worldwide. Yet their productivity and quality are severely compromised by foliar fungal diseases, particularly powdery mildew (PM), downy mildew (DM), and target leaf spot (TLS). While PM and DM have been extensively studied, TLS has emerged as an increasingly prevalent and damaging disease in key production regions, yet it remains comparatively understudied—especially with respect to its molecular basis and comparative pathobiology relative to PM and DM. Current reliance on chemical fungicides is hampered by escalating pathogen resistance and concerns over residual toxicity, whereas conventional breeding approaches face inherent limitations in pyramiding durable, broad-spectrum resistance against multiple pathogens. In this context, cucumber has emerged as a pivotal model species for dissecting foliar disease resistance mechanisms in cucurbits, supported by a high-quality reference genome, extensive resequencing datasets, diverse germplasm collections, and an efficient Agrobacterium-mediated transformation system. Despite these advantages, existing reviews predominantly address PM or DM resistance in isolation; comprehensive syntheses integrating TLS resistance advances—and critically, cross-disease comparisons of genetic architecture, transcriptional reprogramming, and defense signaling—are notably scarce. Furthermore, the translational pipeline—from gene discovery and functional validation to deployment in marker-assisted or genome-edited breeding—lacks systematic evaluation. Here, we provide a focused, cucumber-centered review that (i) synthesizes recent progress in mapping QTLs and GWAS loci, and characterizing key resistance-associated gene families (such as NLRs, RLKs, PR genes) conferring resistance to PM, DM, and TLS; (ii) integrates transcriptomic, epigenomic, and proteomic evidence to delineate conserved versus pathogen-specific host responses; (iii) highlights breakthroughs and unresolved questions in TLS resistance research, including the roles of novel susceptibility factors and non-canonical immune regulators; and (iv) critically assesses bottlenecks in translating resistance genes into practical breeding outcomes—such as linkage drag, functional redundancy, and genotype-by-environment interactions—and proposes empirically grounded strategies for accelerating molecular design of multi-disease-resistant cultivars. Collectively, this review aims to bridge fundamental insights with applied breeding goals, offering a conceptual and strategic framework for integrated management of foliar fungal diseases and the development of durable, broad-spectrum resistance in cucurbits.