Biomarker Research in Solid Carcinoma: Predicting Toxicity and Response Prediction during Treatment with Immune Checkpoint Inhibitors
Group Sylvie Rottey
Project 4
Biomarker Research in Solid Carcinoma: Predicting Toxicity and Response Prediction during Treatment with Immune Checkpoint Inhibitors
Description
In a variety of solid tumors, patients with recurrent/disseminated disease are treated with immune checkpoint inhibitors. The general objective of this research project is to tailor immunotherapy use to the individual patient by developing positive selection criteria (that predict response to the therapy) and negative selection criteria (that predict severe side effects to the therapy) that permit more effective and safer use of this type of therapy. Therefore we aim to construct an extended next generation sequencing-based DNA sequencing gene panel to access mutational burden, smoking signature (C to A transversions), and mutations in DNA repair and immune-response-related genes. This test will be optimized to predict which patients are more likely to respond to ICI. The test should be applicable on formalin-fixed paraffin-embedded (FFPE) material in routine fashion and sensitive enough to be used as a liquid biopsy. Next, whole-transcriptome analysis (including gene expression profiling and mutation analysis) will be performed on the same FFPE biopsy samples to determine the predictive value of this RNA sequencing test and to compare this RNA test with the DNA test. Consequently, immunohistochemical markers, such as PD-L1 and CTLA-4, tumor infiltrating lymphocytes and such will be assessed to determine their predictive value in addition to the sequencing results. Lastly, multiple (peripheral) blood markers will be examined and evaluated before, during and after ICI treatment regarding their predictive value of therapy response and development of IRAEs in a retrospective and prospective manner.
Funding Ageny
Application 2018 call of "Kom Op Tegen Kanker" (spinocellular head and neck cancer and ICI)
Restricted grant from MSD (urothelial carcinoma and ICI) (2018)
Contact
Sylvie Rottey; MD, PhD (Medical Oncology – Ghent University Hospital)
Jo Van Dorpe; MD, PhD (Pathology – Ghent University Hospital)
Liesbeth Ferdinande; MD, PhD (Pathology – Ghent University Hospital)
Paul Clement; MD, PhD (Medical Oncology –University Hospitals Leuven)
Tijl Vermassen; MD, PhD (Medical Oncology – Ghent University Hospital)
Stijn De Keukeleire; MD (Medical Oncology – Ghent University Hospital)