CE17 - Recherche translationnelle en santé

Prediction of response to systemic treatments in hepatocellular carcinoma – SYSTHEC

Submission summary

Background: The combination of immunotherapy (atezolizumab) and anti-angiogenic antibody (bevacizumab) is the standard of care in first line for advanced hepatocellular carcinoma (HCC) whereas tyrosine kinase inhibitors such as sorafenib/lenvatinib are used in second line. However, only a subset of patients benefits from immunotherapy/tyrosine kinase inhibitor and currently no biomarkers are available to guide the sequence of systemic treatments in patients with advanced HCC.

Aims: We aim to identify predictor of response to atezolizumab/bevacizumab based on tumor analysis using a multimodal approach (immune-genome, histology, radiology) and compared them with data in patients treated by tyrosine kinase inhibitors, sorafenib and lenvatinib.

Methodology: We will analyze by whole exome and RNA sequencing 120 HCC samples from patients treated by atezolizumab/bevacizumab and sorafenib in order to identify genetic alterations, transcriptome and immunome profiling associated with response and the results will be validated in a cohort of 110 patients. We will perform histological and immunohistochemical analysis as well as artificial intelligence analysis in 140 HCC samples from patients treated by atezolizumab/bevacizumab or by sorafenib and correlate them with outcomes. An analysis of imaging and radiological features will be performed in all patients and results generated will be validated in a second series of patients. Paired tumor biopsy before and after treatments will be analyzed by immunogenomic analysis in order to characterize the tumor evolution under anti-PD1 therapy (50 patients) and lenvatinib (50 patients) included in two phase 2 clinical trials.

Expected results: We want to propose precision medicine for patients with advanced HCC adapted to immunogenomic profiling of the tumor and predict the response/resistance to immunotherapy and tyrosine kinase inhibitor

Project coordinator

Monsieur Jean Charles Nault (CENTRE DE RECHERCHE DES CORDELIERS)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CRC CENTRE DE RECHERCHE DES CORDELIERS

Help of the ANR 344,932 euros
Beginning and duration of the scientific project: December 2022 - 36 Months

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