The first seminar will take place on the upcoming Wednesday, January 25th , and will be held by Kushtrim Kryeziu, Department of Molecular Oncology.
The title of his talk is "Ex vivo treatment modeling of metastatic colorectal cancers for personalized oncology".
The seminar will start at 12:00 in Auditorium 1, Research building (K).
Colorectal cancer (CRC) patients have limited treatment options due to tumor heterogeneity and lack of biomarkers. To address this issue, we have generated a living biobank of more than 230 patient-derived tumor organoids (PDOs) from liver metastases of more than 110 patients treated by hepatic resection for metastatic colorectal cancer (CRC) at Oslo University Hospital. The biobank includes many tumor organoids derived from multiple synchronous lesions and recurrent lesions sampled at hepatic re-resections. All PDOs have been screened for sensitivity to a customized drug library incorporating approved single agents and combinations of drugs with promising clinical activity against CRC. Furthermore, gene expression profiles and mutations in selected genes have been analyzed in subsets of the PDOs and their corresponding tumor tissue samples for pharmacogenomic associations. As expected, most PDOs were TP53 mutated and associated with multidrug resistance, whereas a few TP53 wild-types confer sensitivity towards PARP inhibition. A few targeted agents displayed outlier activities in a subset of patients with genomic alterations that increased vulnerabilities towards known associating targeted drugs. Based on the established translational platform, a prospective phase 2 clinical study started recently at Oslo University Hospital to guide systemic therapy for patients with metastatic CRC by personalized pharmacogenomics measured ex vivo in PDOs in our lab. Summary data from the retrospective PDO panel as well as patient cases with interventions based on the drug screen of the tumor avatars will be presented.