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Session: Parallel session 10 - Health and biological sciences

Proteomic profiling can predict the response to first-line treatment in patients with advanced hepatocellular carcinoma

Adèle DELAMARRE2,7, Giovanni BÉNARD3, Claude LALOU3, Benoît PINSON4, Paulette BIOULAC-SAGE2, Caroline TOULOUSE5, Audrey MORISSET5, Jérôme BOURSIER5, Brigitte LE BAIL2,6, Frédéric SALTEL1,2, Anne-Aurélie RAYMOND1,2, Marie DECRAECKER2,5, Jean-Frédéric BLANC2,5, Sylvaine DI TOMMASO1, Cyril DOURTHE1,2, Jean-William DUPUY1, Nathalie ALLAIN2, Isabelle MAHOUCHE2, Julie GIRAUD2

1Univ. Bordeaux, CNRS, INSERM, TBM-Core, US5, UAR 3427, OncoProt, Bordeaux, France
2Univ.Bordeaux, Inserm UMR1312 BoRdeaux Institute of onCology (BRIC), Bordeaux, France
3Univ. Bordeaux, INSERM, MRGM, U1211, Bordeaux, France
4Univ. Bordeaux, CNRS, INSERM, TBM-Core, US5, UAR 3427, SAM, Bordeaux, France
5Department of Hepatology and Oncology, Angers University Hospital, Angers , France
6Department of Pathology, Bordeaux University Hospital, Bordeaux, France
7Department of Hepatology and Oncology, Bordeaux University Hospital, Inserm CIC 1401, Bordeaux, France

Background & Aims: Access to personalized medicine for cancer sufferers is one of the great challenges of our time. Genetic mutations in tumors now make it possible to prioritize the treatment of certain cancers, but this is not always possible. Liver cancer is a case in point. Hepatocellular carcinoma (HCC) is the most common form of liver cancer but, due to late diagnosis, the prognosis is extremely poor and the majority of cases are advanced HCC, which are only eligible for palliative systemic therapies. After a decade of exclusive sorafenib monotherapy, with a response rate of < 10%, the advent of new combinations including immunotherapies represents a revolution in the management of HCC. The combination of atezolizumab/bevacizumab is recommended as the first-line systemic treatment for HCC, with a response rate of no more than 30%. Additionally, less than 25% of non-responding patients are eligible for second-line treatment. However, there are currently no predictive factors for response to these different treatment options. We hypothesized that the proteome of pre-treatment biopsies contained the information needed to predict response to cancer treatment and to identify the biological pathways involved in treatment response.

Approach & Results: Using high-resolution mass spectrometry, we compared the proteomic profiles of 40 patients with advanced HCC. We showed that these proteomic profiles enabled us to differentiate between patients who responded to treatment and those who progressed. We identified biological pathways involved in treatment response, in particular a change in tumor energy metabolism could explain resistance to the first-line immunotherapy combination atezolizumab/bevacizumab, which we confirmed in 3D cell models.

Conclusions: This study shows that the proteomic profile of a liver biopsy can be a promising tool for predicting response to treatment of advanced HCC and can optimize patient management.