Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer

Poorly cohesive gastric cancer (PCGC) represents a biologically distinct subtype of gastric cancer, characterized by diffuse growth, marked intratumoral heterogeneity, and a consistently worse prognosis compared with other histological subtypes. Despite advances in pathological classification and molecular profiling, treatment strategies remain largely independent of histological subtype, and no specific therapeutic approaches have been established for PCGC. In this review, we summarize current evidence on the biological features, diagnostic challenges, and emerging therapeutic strategies, with a focus on novel targeted agents and innovative treatment platforms. Recent years have witnessed the development of therapies directed against specific molecular targets, including HER2, PD-L1, CLDN18.2, FGFR2b, and TROP2, as well as the introduction of antibody-drug conjugates and bispecific antibodies, progressively expanding the therapeutic landscape of gastric cancer. However, their clinical impact in poorly cohesive tumors remains to be fully defined. In parallel, advances in digital pathology, artificial intelligence, and multi-omics approaches are providing new opportunities to improve diagnostic reproducibility, refine prognostic stratification, and support personalized treatment strategies by integrating histomorphological and molecular tumor features. Overall, the convergence of novel therapeutic strategies and advanced diagnostic technologies may pave the way toward a more precise and biologically informed management of PCGC, although further validation and integration into clinical practice are required.