TY  - JOUR
A1  - Altieri, Barbara
A1  - Sbiera, Silviu
A1  - Herterich, Sabine
A1  - De Francia, Silvia
A1  - Della Casa, Silvia
A1  - Calabrese, Anna
A1  - Pontecorvi, Alfredo
A1  - Quinkler, Marcus
A1  - Kienitz, Tina
A1  - Mannelli, Massimo
A1  - Canu, Letizia
A1  - Angelousi, Anna
A1  - Chortis, Vasileios
A1  - Kroiss, Matthias
A1  - Terzolo, Massimo
A1  - Fassnacht, Martin
A1  - Ronchi, Cristina L.
T1  - Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study
JF  - Cancers
N2  - Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2% vs 51.7%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55% of patients with CYP2B6*6 vs. 28.2% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane.
KW  - adrenocortical carcinoma
KW  - mitotane
KW  - CYP2W1
KW  - CYP2B6
KW  - SNP
KW  - biomarker
KW  - predictive marker
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200565
SN  - 2072-6694
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Doghman-Bouguerra, Mabrouka
A1  - Finetti, Pascal
A1  - Durand, Nelly
A1  - Parise, Ivy Zortéa S.
A1  - Sbiera, Silviu
A1  - Cantini, Giulia
A1  - Canu, Letizia
A1  - Hescot, Ségolène
A1  - Figueiredo, Mirna M. O.
A1  - Komechen, Heloisa
A1  - Sbiera, Iuliu
A1  - Nesi, Gabriella
A1  - Paci, Angelo
A1  - Al Ghuzlan, Abir
A1  - Birnbaum, Daniel
A1  - Baudin, Eric
A1  - Luconi, Michaela
A1  - Fassnacht, Martin
A1  - Figueiredo, Bonald C.
A1  - Bertucci, François
A1  - Lalli, Enzo
T1  - Cancer-testis antigen FATE1 expression in adrenocortical tumors is associated with a pervasive autoimmune response and is a marker of malignancy in adult, but not children, ACC
JF  - Cancers
N2  - The SF-1 transcription factor target gene FATE1 encodes a cancer-testis antigen that has an important role in regulating apoptosis and response to chemotherapy in adrenocortical carcinoma (ACC) cells. Autoantibodies directed against FATE1 were previously detected in patients with hepatocellular carcinoma. In this study, we investigated the prevalence of circulating anti-FATE1 antibodies in pediatric and adult patients with adrenocortical tumors using three different methods (immunofluorescence, ELISA and Western blot). Our results show that a pervasive anti-FATE1 immune response is present in those patients. Furthermore, FATE1 expression is a robust prognostic indicator in adult patients with ACC and is associated with increased steroidogenic and decreased immune response gene expression. These data can open perspectives for novel strategies in ACC immunotherapy.
KW  - adrenocortical carcinoma
KW  - cancer-testis antigens
KW  - autoantibodies
KW  - immune response
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203211
SN  - 2072-6694
VL  - 12
IS  - 3
ER  -