Response prediction in metastatic clear-cell renal cell carcinoma treated with angiogenesis and/or immune checkpoint inhibitors

Angiogenesis inhibitors (VEGFR-TKIs) and immune checkpoint inhibitors (ICPIs) are efficient therapies for metastatic clear-cell renal cell carcinoma (ccRCC). From 2020 on, standard first-line therapy will be the combination of two ICPIs (nivolumab/ipilimumab) or the combination of one ICPI (pembrolizumab or avelumab) and one VEGFR-TKI (axitinib). VEGFR-TKIs in monotherapy (cabozantinb, axitinib) are used from second-line on. However, few predictive biomarkers are available. Sarcomatoid tumors respond better on ICPIs than on VEGFR-TKIs. VEGFR-TKIs work better in hypervascular and indolent tumors than in tumors with few neoangiogenesis and aggressive tumors. More precise predictive biomarkers would allow a more efficient use of these expensive therapies and to save adverse events in patients in whom these therapies do not work. Our research team has developed a molecular classification of ccRCC with a prognostic and a predictive impact. The aim of this research project is to discover additional predictive biomarkers for ICPIs and for VEGFR-TKIs on top of the molecular classification. We will study (A) HLA-subtypes of the patients suffering ccRCC, (B) mutations in DNA damage repair genes, (C) immune cells and proteins involved in the antitumoral immune reaction and the immune suppressive micro-environment as well as (D) specific characteristics of angiogenesis (such as FGFR2) and mechanisms of resistance to angiogenesis inhibitors (such as cMET).