The potential of personalized cancer spheroids in precision therapy

The clinical implementation of precision oncology remains challenged by intratumoral heterogeneity, complex tumor microenvironment interactions, and the limited predictive value of conventional preclinical models. 3D cancer spheroids have emerged as physiologically relevant platforms that closely mimic in vivo tumor architecture, cellular heterogeneity, hypoxic gradients, and treatment resistance mechanisms. This review highlights the growing role of cancer spheroids in drug panel testing and their application in personalized therapeutic decision-making across diverse malignancies, including breast, colorectal, ovarian, lung, head and neck, and brain cancers. Patient-derived spheroids and multicellular co-culture models preserve critical tumor-stroma and tumor-immune interactions, enabling clinically meaningful evaluation of chemotherapeutic agents, targeted therapies, immunotherapies, radiosensitizers, and combination treatment strategies. Drug panels assessed using spheroid platforms encompass platinum-based agents, EGFR and VEGF inhibitors, PARP inhibitors, immune checkpoint inhibitors, kinase inhibitors, antibody-drug conjugates, and emerging pathway-directed therapeutics. Accumulating evidence suggests that spheroid-based drug testing has the potential to recapitulate clinically relevant tumor characteristics and treatment responses and may serve as a useful preclinical approach for evaluating drug sensitivity, exploring resistance mechanisms, and assessing biomarker-associated responses within clinically relevant timeframes. Recent advances in high-throughput screening, microfluidic technologies, organ-on-chip systems, automated imaging, and artificial intelligence-driven analytics have further improved the scalability, reproducibility, and translational utility of these models. The review also discusses the current limitations, standardization challenges, and ethical considerations associated with spheroid-based drug testing. Collectively, personalized cancer spheroids represent a promising approach linking experimental oncology with precision medicine research, with potential applications in individualized drug testing and treatment optimization.