Incorporating tumor genomic profiling and drug screening through circulating tumor cell- derived organoids into clinical practice for the management of Gastrointestinal Cancers

Abstract Purpose Precision medicine aims to revolutionize healthcare by tailoring treatment regimens. The study aimed to integrate comprehensive tumor genomic profiling (CTGP) by targeted-gene panel sequencing and drug screening by circulating tumor cell-derived organoids (CTOs) into clinical practice for the treatment of gastrointestinal (GI) cancers. Methods Nine patients with various GI cancers underwent CTGP and CTO drug sensitivity testing. CTGP results guided targeted therapy and immunotherapy, while CTO drug sensitivity predicted response to chemotherapy and targeted agents. The drug recommendations from two platforms were correlated with the treatment response from the suggested medications retrospectively. Results Five patients received therapies aligned with CTGP, including HER2-targeted treatment, immunotherapy, and BRAF/MEK dual inhibition, showing positive responses. CTO drug sensitivity predicted progression under regorafenib (low potential benefit) and good response to chemotherapy with high potential benefit. The combination of CTGP and CTO drug sensitivity may exhibit significant correlation with clinical outcomes during treatment with candidate drugs, demonstrating a sensitivity of 79% and an accuracy of 75%. This encompasses various treatment modalities such as chemotherapy, targeted therapy, and immunotherapy. Conclusion The present investigation elucidated the integration of CTGP and CTO drug sensitivity screening into clinical practice in a complementary manner, showcasing a significant correlation between testing results and treatment response. Additional prospective evaluation of these two testing modalities in a large cohort is warranted to confirm whether the inclusion of CTO drug sensitivity screening confers enhanced survival benefits compared to utilizing CTGP alone.