February 9, 2023

High Throughput Personalized Treatment Screening for Pancreatic Cancer Patients

2nd Call, TPdF

Short Summary

This study explores the potential of screening a large panel of FDA-approved drugs for effective new treatment combinations in pancreatic cancer. We expect that we will be able to validate hits from our screen in our patient derived organoid biobank, and to use this FDA-approved drug in a clinical trial for pancreatic cancer upon the end of the project. Additionally, the mutational and/or gene expression profile of responders in organoids would help to identify suitable patients in the clinics.

Goals

The goals of this project are: a) Identification of FDA approved drugs for off label pancreatic cancer treatment; b) Identification of biomarkers to predict efficacy of the novel off label pancreatic cancer drugs.

Significance

Pancreatic cancer is a highly aggressive malignancy with a mortality rate above 98%. Currently the only curative therapy for pancreatic cancer is surgical resection. Due to late disease detection, this is only suitable for about 20% of all patients. Therapeutic options for locally advanced or metastatic pancreatic cancer are therefore needed. Importantly, for pancreatic cancer there is no good standard of care after a first chemotherapy (in average 11 month after diagnosis), and thus the hurdle to test experimental compounds is very low.

Background

In the past, the lack of suitable in vitro pancreatic cancer models for drug testing hindered the identification of effective therapies. In recent years, patient derived organoids from tumor tissues have been developed. Compared to 2D cancer cells lines, these models better incorporate the cellular dynamics and phenotypes of pancreatic cancer. Together with our clinical partners we built a biobank over 30 patient-derived organoid lines and established a robust automated high-throughput screening protocol testing over 1’000 compounds simultaneously.

Publications

Christian K Hirt et al Drug screening and genome editing in human pancreatic cancer organoids identifies drug-gene interactions and candidates for off-label treatment. Cell Genom 2022 Feb;2(2):100095. doi: 10.1016/j.xgen.2022.100095.