Project description:Patient-derived endometrial cancer organoids. The data was used to compare gene expression profile between organoids, and to explore whether an organoid-derived gene signature could predict disease outcomes in independent patient cohorts.
Project description:Colorectal cancer (CRC) is a commonly occurring cancer worldwide. Metastasis and recurrence are the major causes of cancer-related death. CRC progression is a multistep process, and extensive efforts have been made to identify the genomic and transcriptomic alterations that occur during this process. However, whether primary tumors and metastatic lesions possess distinct biological features remains unclear. We established 74 patient-derived organoids (PDOs) from primary tumors and patient-matched metastatic and recurrent lesions.
Project description:Patient-derived tumor organoids are clinically relevant ex vivo models that preserve key molecular and functional characteristics of the original tumor. The Freeze-O Organoid Biobank at the University Medical Center Freiburg is an integrated and translational platform to support Molecular Tumor Board-guided precision oncology by facilitating functional PDTO-based drug test. Informing personalized treatment strategies is often limited by the availability, quality, and quantity of patient-derived material. A major challenge is to provide clinically actionable information in time to inform treatment decisions, in particular for patients with metastatic disease. Here, we demonstrate rapid PDTO establishment from a lung metastasis of a patient with metastatic colorectal cancer. This enabled patient-specific drug tests and whole exome sequencing, which had not been feasible from the initial patient material. Using these PDTOs, we screened ten clinically relevant drugs, mainly targeting the ERK pathway based on the identified KRASG12V mutation. Single, combination, and long-term treatment assays revealed a patient-specific treatment rationale for vertical EGFR/HER-MEK1/2 inhibition using Lapatinib and Trametinib. These findings were presented to the Molecular Tumor Board; however, the patient succumbed to the severity of metastatic colorectal cancer. Earlier and routine integration of organoid-based drug testing into MTB processes could help identify personalized treatment strategies more efficiently. In particular, patients with severe metastatic cancer should be enrolled early enough to provide decisive information in a clinically actionable time frame.