Abstract
Abstract Patient-derived tumoroids have emerged as promising models for evaluating patient-specific responses to anti-cancer therapies, yet their clinical adoption remains limited. While the reasons for this limited implementation are not fully elucidated, several are known and can be addressed: (1) lack of standardized protocols for tumoroid cultivation and drug exposure complicating cross-lab comparisons, (2) labor- and time-intensive cultivation procedures conflicting with clinical guidelines for timely therapy initiation, (3) prevalent use of destructive endpoint assays restricting subsequent analyses and proper growth-rate correction, and (4) poorly defined criteria for classifying tumoroid drug sensitivity that are not linked to clinical outcomes, leading to suboptimal treatment allocation in prospective studies. In this study, we developed two classifiers for assessing colorectal tumoroid sensitivity to oxaliplatin and SN-38 based on historical response rates for patients with colorectal cancer. Utilizing longitudinal, label-free confocal imaging, these classifiers offer a non-destructive method that corrects for growth-rate variations and preserves patient-derived material for further analysis. Currently, these classifiers are undergoing evaluation in a prospective clinical trial to determine the feasibility of incorporating tumoroid-based drug screening into clinical decision-making. This approach lays the groundwork for next-generation molecular tumor boards, enabling anti-cancer treatment decisions informed by integrated functional assays and biomarkers.