JCP-265

Drug screening technologies are experimental and computational strategies used to identify small molecules or chemical probes that modulate a defined molecular target, signaling pathway, cellular phenotype, disease model, or patient-derived response profile. High-throughput screening tests many compounds in miniaturized assay formats, while quantitative high-throughput screening tests compounds across concentration ranges so that potency and efficacy can be inferred from concentration-response behavior rather than from a single-point signal. The core biological function of a drug-screening strategy is to connect compound exposure with measurable pathway activity, target modulation, cell-state change, viability, cytotoxicity, morphology, or disease-relevant phenotype. Assay performance must be evaluated before screening because hit identification depends on the separation between positive and negative controls, control variability, plate effects, outliers, and the statistical framework

Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi