Akademik Veri Yönetim Sistemi
Organoids, cilt.5, sa.2, ss.1-20, 2026 (Scopus)
Treatment-refractory rectal cancer liver metastasis represents a major therapeutic challenge, particularly in the absence of actionable genomic biomarkers. Functional precision oncology approaches integrating genomic profiling with patient-derived organoid (PDO) drug testing may provide biologically informed therapeutic prioritization. A 50-year-old female patient with KRAS/TP53-mutant, microsatellite-stable (MSS) rectal adenocarcinoma refractory to FOLFIRINOX was enrolled. A liver metastasis from a treatment-refractory rectal cancer patient was processed to establish three-dimensional patient-derived organoids. Histopathological concordance was assessed using H&E and p53 immunohistochemistry. Comprehensive genomic profiling was performed using a 637-gene targeted nextgeneration sequencing panel, enabling detection of single-nucleotide variants, indels, copy number variations, microsatellite instability, and tumor mutational burden. Functional drug sensitivity profiling was conducted in parallel 2D and 3D platforms using a customized 17-agent panel, followed by exploratory combinatorial validation. The organoids demonstrated high phenotypic and genomic concordance with the parental tumor, preserving key driver alterations (KRASˆA146T, TP53ˆR175H, APC frameshifts, CCNE1 amplification), microsatellite stability, and low tumor mutational burden (TMB: 6.37 mut/Mb). Functional screening identified selective sensitivity to bevacizumab (IC50: 0.130 µM), doxorubicin (IC50: 0.570 µM), carboplatin (IC50: 0.950 µM), and topotecan (IC50: 1.600 µM) in the 3D organoid model, with consistent cross-platform validation. An exploratory combination assay further supported enhanced viability suppression under bevacizumab-based regimens. Critically, at the time of manuscript preparation, the patient demonstrated radiological disease stabilization under bevacizumab plus trastuzumab deruxtecan, consistent with the organoid-derived response profile. These findings highlight the capacity of integrated genomic and organoid-based profiling to uncover therapeutic vulnerabilities beyond standard biomarker assessment. This proof-of-concept case report study demonstrates the feasibility and translational relevance of an established organoid-based functional precision oncology platform for therapeutic prioritization in metastatic rectal cancer.