Stem Cell-Derived Organoids for Cancer Therapy: Precision Medicine and Drug Selection

Millions of new cancer cases and deaths worldwide annually demonstrate the pressing need for predictive preclinical models that go beyond standard two-dimensional (2D) cultures and animal systems. Recent developments in three-dimensional (3D) organoid technology have yielded a powerful platform for generating patient-specific mini-organ models that faithfully recapitulate primary tumors at the genetic, phenotypic, and architectural levels. Organoids retain functional fidelity by preserving key stem cell signaling pathways, including Wnt, Notch, and Hippo, making them robust platforms for disease modeling and high-throughput drug screening. This review describes representative organoid systems, ranging from patient-derived organoids (PDOs) to induced pluripotent stem cell (iPSC)-derived organoids, that serve as disease-specific “avatars” for personalized therapeutics. Predictive accuracy rates greater than 90% have been shown in clinical studies, providing evidence for the relevance of organoids in functional precision medicine. In addition to drug discovery, the extended use of organoids in regenerative oncology can provide a unique regulatory mechanism by selectively targeting CSCs and enhancing tissue repair after cytotoxic treatments. Recent advances in organoid-on-a-chip platforms, 3D bioprinting, and artificial intelligence (AI) address critical challenges involving vascularization, immune system integration, and scalability. With the advent of standardized, GMP-compliant platforms and recent regulatory initiatives, such as the FDA Modernization Act 2.0, organoids are well-positioned to support next-generation cancer research and therapy. This review aims to bridge the gap between stem cell-derived organoids (SCDOs), providing a fully humanized platform for preclinical cancer modeling and their clinical application, and to discuss their potential to advance ethically guided, personalized cancer therapeutics with improved predictive and translational power.