Abstract LB-A09: Predicting PARPi sensitivity in patient derived ex vivo 3D tumor cultures

Abstract

Abstract Ex vivo culture of patient derived tumor material has broad applications including functional testing to support treatment decisions, as well as testing drugs in development. Because average therapeutic response rates are low, there is a need for clinical tools to predict treatment response. Such tools may also reduce overtreatment and provide alternatives when treatment options are exhausted. Here we present data for 3D tumor cultures focusing on standard chemotherapy in combinations with targeted therapy, namely PARPi. By embedding and optimizing growth for small amounts of heterogeneous tumor material in extracellular matrix protein hydrogels, we have generated 3D tumor cultures from various cancer indications. Initiated from both fresh and cryopreserved material, tumor cultures are seeded into 384 well plates and exposed to standard-of-care therapies, targeted therapies and drug combinations. An automated high content screening platform measures cell and tissue morphology, and reports responses such as tumor cell killing, growth arrest and local invasion. Depending on the tumor type and drug mechanism of action, morphological features are selected as standard read-outs for the response. We will present results of proof-of-concept experiments that aim to compare drug sensitivity of tumor cultures with treatment responses in the clinic. Tumor material of gastric, endometrial, cervical, and ovarian cancer patients was used to generate 3D cultures, which were subsequently tested for drug sensitivity. Patient-dependent responses are identified for treatment schedules including platinum-based drugs, taxanes, anthracyclines and 5-FU. In addition, responses to drugs that are not (yet) considered standard of care (PARP inhibitors) were measured. In conclusion, our technology can determine drug sensitivities of 3D cultured tumor tissues. This allows patient-specific treatment responses to standard-of-care drugs to be determined. In addition, this material can be used to test experimental drugs currently in development and in clinical studies. Ongoing proof-of-concept trials will reveal the correlation of our in vitro test with treatment responses in the clinic. Keywords; in vitro diagnostic; organoids; tumor cultures; drug sensitivity testing. Citation Format: Sander Basten, Bram Herpers, Kuan Yan, Willemijn Vader, Leo Price. Predicting PARPi sensitivity in patient derived ex vivo 3D tumor cultures [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A09.