Advancements in organoid models emulating metastatic niches.

Abstract

Metastases cause most cancer-related deaths, underscoring the need for therapies targeting metastatic stages, including the tumor microenvironment. Yet translating biological insights into treatments remains difficult. Preclinical metastasis research largely relies on rodent models, which have species-specific limitations and are incompatible with large-scale perturbation screens in a human context. Human organoids aim to emulate organ microenvironments in vitro and, when cocultured with cancer cells, can provide complementary models. These 'chimeroids' may enable scalable studies of cancer-microenvironment interactions and support genetic and pharmacological screens to discover new targets, offering insights into the final, often lethal step of metastasis-tissue colonization. This review summarizes advances in stem cell-derived organoid models for organs frequently affected by solid tumor metastases, including the brain, lung, liver, and bone, and evaluates their ability to recreate physiologically relevant niches for studying cancer cell adaptation and colonization.