Short summary

We want to explore if it is possible to use patient derived tumoroids to predict effect or lack of effect from standard chemotherapy to patients with metastatic pancreatic cancer. Furthermore, we want to test the feasibility of selecting second-line therapy based on pre-treatment biopsies.

Rationale

Chemotherapy treatment of cancer remains a challenge due to the molecular and functional heterogeneity displayed by tumors originating from the same cell type. The pronounced heterogeneity makes it difficult for oncologists to devise an effective therapeutic strategy for the individual patient. One approach to improving treatment efficacy is to test the chemosensitivity of cancer cells obtained from the patient's tumor prior to treatment initiation. 3D culture represents a promising method for modelling of patient tumors in vitro. Preliminary studies have shown that colorectal cancer cells isolated from patient derived biopsies can be cultured as spheroids with a high success rate and remain viable for at least 10 days. Furthermore, chemosensitivity screening using spheroids from different colorectal cancer patients has demonstrated individual response profiles. Molecular changes in biopsy and in biopsy-derived tumoroids are maintained. 

Pancreatic cancer is one of the most common and most deadly cancers in Europe. The standard of care to patients with non-resectable or metastatic spread is chemotherapy with gemcitabine, nab-paclitaxel, 5-flourouracil and derivates, oxaliplatin and irinotecan. When patients progress after exposure to one or more of these drugs as first-line therapy, the standard is best supportive care or enrollment in clinical trials. No randomized trials have proved survival benefit from second-line therapy. Beside the aforementioned drugs, many other drugs have a sound biological rationale for potential effect and have shown some level of activity in pancreatic cancer in early phase trials but without clinical impact in unselected patients.

We want to explore if it is possible to predict effect or lack of effect from first-line treatment. Furthermore, we want to test the feasibility of selecting second-line therapy based on pre-treatment biopsies. 

Description of the cohort

Patients, men and women, with metastatic pancreatic cancer. 

Data and biological material

Biopsy from metastatic site, most often the liver. Longitudinal blood samples. 

Collaborating researchers and departments

Departments of Radiology, Pathology, Genetics and Biochemistry, Vejle Hospital

The company 2cureX, Copenhagen University

• Professor Ole Thastrup