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Despite the advances in detection, diagnosis, and treatments, cancer remains a lethal disease, claiming the lives of more than 600,000 people in the United States alone in 2024. To accelerate the development of new therapeutic strategies with improved responses, significant efforts have been made to develop microfabricated in vitro models of tumor microenvironments (TMEs) that address the limitations of animal-based cancer models. These models incorporate several advanced tissue engineering techniques to better reflect the organ- and patient-specific TMEs. Additionally, microfabricated models integrated with next-generation single-cell omics technologies provide unprecedented insights into patient's cellular and molecular heterogeneity and complexity. This review provides an overview of the recent understanding of cancer development and outlines the key TME elements that can be captured in microfabricated models to enhance their physiological relevance. We highlight the recent advances in microfabricated cancer models that reflect the unique characteristics of their organs of origin or sites of dissemination.
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