TY  - JOUR
A1  - Schrama, David
A1  - Ugurel, Selma
A1  - Sucker, Antje
A1  - Ritter, Cathrin
A1  - Zapatka, Marc
A1  - Schadendorf, Dirk
A1  - Becker, Jürgen Christian
T1  - STAT3 Single Nucleotide Polymorphism rs4796793 SNP Does Not Correlate with Response to Adjuvant IFNα Therapy in Stage III Melanoma Patients
JF  - Frontiers in Medicine
N2  - Interferon alpha (IFNα) is approved for adjuvant treatment of stage III melanoma in Europe and the US. Its clinical efficacy, however, is restricted to a subpopulation of patients while side effects occur in most of treated patients. Thus, the identification of predictive biomarkers would be highly beneficial to improve the benefit to risk ratio. In this regard, STAT3 is important for signaling of the IFNα receptor. Moreover, the STAT3 single-nucleotide polymorphism (SNP) rs4796793 has recently been reported to be associated with IFNα sensitivity in metastatic renal cell carcinoma. To translate this notion to melanoma, we scrutinized the impact of rs4796793 functionally and clinically in this cancer. Interestingly, melanoma cells carrying the minor allele of rs4796793 were the most sensitive to IFNα in vitro. However, we did not detect a correlation between SNP genotype and STAT3 mRNA expression for either melanoma cells or for peripheral blood lymphocytes. Next, we analyzed the impact of rs4796793 on the clinical outcome of 259 stage III melanoma patients of which one-third had received adjuvant IFNα treatment. These analyses did not reveal a significant association between the STAT3 rs4796793 SNP and patients' progression free or overall survival when IFNα treated and untreated patients were compared. In conclusion, STAT3 rs4796793 SNP is no predictive marker for the efficacy of adjuvant IFNα treatment in melanoma patients.
KW  - predictive marker
KW  - single nucleotide polymorphism
KW  - melanoma
KW  - interferon
KW  - STAT3
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120602
SN  - 2296-858X
VL  - 1
IS  - 47
ER  - 
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  -