Genetic variants associated with Fabry disease progression despite enzyme replacement therapy

Scionti, Francesca; Martino, Maria Teresa Di; Sestito, Simona; Nicoletti, Angela; Falvo, F.; Roppa, K; Arbitrio, Mariamena; Guzzi, Pietro Hiram; Agapito, Giuseppe; Pisani, Antonio; Riccio, Eleonora; Concolino, Daniela; Pensabene, Licia

doi:10.18632/oncotarget.22505

Cited by 34 publications

(19 citation statements)

References 36 publications

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“…In the esophageal muscle tissue, 2 single-nucleotide polymorphisms (rs1126671 and rs1800759) were associated with lower ADH4 expression levels in fibroblasts [ 44 ]. The ADH4 gene encodes the π subunit in humans and can metabolize many substances, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products [ 45 ]. The ADH5 gene encodes the χ subunit, which participates in the metabolism of alcohols and aldehydes [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

et al. 2018

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BackgroundNon-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The relationships of alcohol dehydrogenase (ADH) enzymes, encoded by the genes ADH1 (1A), ADH1B (ADH2), ADH1C (ADH3), ADH4, ADH5, ADH6, and ADH7, with NSCLC have not been studied. The aim of this study was to explore the associations between NSCLC prognosis and the expression patterns of ADH family members.Material/MethodsThe online resource Metabolic gEne RApid Visualizer was used to assess the expression patterns of ADH family members in normal and primary lung tumor tissues. The GeneMANIA plugin of Cytoscape software and STRING website were used to evaluate the relationships of the 7 ADH family members at the gene and protein levels. Gene ontology enrichment analysis and KEGG pathway analysis were performed using DAVID. The online website Kaplan-Meier Plotter was used to construct survival curves between NSCLC and ADH isoforms.ResultsThe prognosis of patients with high expression levels of the ADH1B, ADH1C, ADH4, and ADH5 genes was better than those with low expression in adenocarcinoma and all (containing adenocarcinoma and squamous cell cancer) histological types (all P<0.05). Low expression of ADH7 was associated with a better prognosis in patients with both the adenocarcinoma and squamous cell cancer histological types (P=9e-05). Moreover, expression of ADH family members was associated with smoking status, clinical stage, and chemotherapy status.ConclusionsADH1B, ADH1C, ADH4, ADH5, and ADH7 appear to be useful biomarkers for the prognosis of NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

et al. 2018

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“…Conversely, in the subgroup analysis conducted for 3-4 toxicity grades or SAE, the safety profile appears deeply unbalanced on different PARPis and in particular niraparib reported a relevant haematologic toxicity. It would be interesting to correlate these events with pharmaco-genomics personalized molecular profiles by the use of dedicated platforms (Arbitrio et al, 2016a, b;Di Martino et al, 2011a, b;Di Martino et al, 2016;Guzzi et al, 2012;Scionti et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis

Staropoli

Ciliberto

Giudice

et al. 2018

Critical Reviews in Oncology/Hematology

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Introduction: Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. Patients and Methods: Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings. We considered the January 2008-April 2018 time frame. Progression free survival (PFS) was the primary end-point, toxicities were secondary end-points. Hazard ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3-4 toxicity rates, were extracted from retrieved studies and included in the current analysis. Meta-analysis was carried out by the fixed and random effect models. We conducted this metaanalysis to also compare indirectly the efficacy of different PARPis in EOC patients. Results: Five randomized trials for a total of 1839 patients were selected and included in the final analysis. In particular, we evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), respectively. Regarding safety profile, no significant differences were detected in all grade toxicities, however, taking into account 3-4 grade toxicities and SAEs (severe adverse events), we show that rucaparib-treated patients reported major abdominal pain events, while niraparib-treated patients were associated with the highest percentage of haematological toxicities, hypothesizing a drug effect for the safety analysis. In the indirect comparisons, significant differences were not detected on PFS for the different agents. Conclusions: We confirm a significant benefit in survival outcome of PARPis for EOC patients with a "class effect" on the bases of narrow CI and indirect comparisons in the different groups. Therefore, we underline that this strategy is of special value in BRCA-mutated patients because genetic testing allows best patient selection for all PARPis with the added value of individualized prevention in familiars. 1. Background Among epithelial ovarian cancer (EOC) patients, women with genetic predisposition show an early onset of disease. Rare high penetrant mutations in BRCA1 and BRCA2 genes greatly increase lifetime risk and account for the majority of hereditary cases, 10%-15% of all cases. These women have a 40-60% lifetime risk of EOC (44% in BRCA1 families and 27% in BRCA2 families, respectively) (Mavaddat et al., 2012; Xu et al., 2017). The gold standard first-line treatment is still based on the combination of carboplatin/paclitaxel (du Bois et al., 1997; Jayson et al., 2014). The management of recurrent disease strictly depends on

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“…The first aim of our study was the identification of genetic variants in ADME genes as candidate predictive biomarkers of grades ≥ 2−3‐TrPN in taxane‐treated patients with BC. DMET array in a PGx scenario represents a valid approach to study agnostically, simultaneously, and in a small population, a predefined list panel of genetic variants in 231 ADME genes, powerful for common and uncommon disease …”

Section: Discussionmentioning

confidence: 99%

“…DMET array in a PGx scenario represents a valid approach to study agnostically, simultaneously, and in a small population, a predefined list panel of genetic variants in 231 ADME genes, powerful for common and uncommon disease. [10][11][12] We performed a case-control study in an LS of 79 patients with BC, and we identified 5 SNPs mapping in 2 genes, NR1I3 and UGT2B7 , statistically associated with protection from grades ≥ 2−3-TrPN. By ROC curves, we validated the grades ≥ 2−3-TrPN-related biomarkers in an independent series of 54 patients with BC.…”

Section: Discussionmentioning

confidence: 99%

Polymorphic Variants in NR1I3 and UGT2B7 Predict Taxane Neurotoxicity and Have Prognostic Relevance in Patients With Breast Cancer: A Case‐Control Study

Arbitrio

Scionti

Altomare

et al. 2019

Clin Pharma and Therapeutics

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Taxane‐related peripheral neuropathy (TrPN) is a dose‐limiting toxicity with important interindividual variability. Genetic polymorphisms in absorption, distribution, metabolism, and excretion (ADME) genes may account for variability in drug efficacy and/or toxicity. By the use of Affymetrix drug‐metabolizing enzyme and transporter microarray platform, in a retrospective case‐control study, the correlation between ADME polymorphic variants and grades ≥ 2−3‐TrPN was investigated. In a breast cancer (BC) training set, five single‐nucleotide polymorphisms in NR1I3 and UDP‐glucuronosyltransferase (UGT)2B7 genes were correlated to grades ≥ 2−3‐TrPN protection. By receiver operating characteristic curves, the grades ≥ 2−3‐TrPN‐related candidate biomarkers in an independent series of 54 patients with BC (17 cases and 37 controls) were validated. NR1I3 was correlated to paclitaxel‐TrPN and UGT2B7 to docetaxel‐TrPN. Moreover, a genetic signature of prognostic relevance for BC outcome was found. Our findings might have potential relevance for personalized management of patients with BC for prevention of treatment failure in ultrametabolizer genetic variants.

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Genetic variants associated with Fabry disease progression despite enzyme replacement therapy

Cited by 34 publications

References 36 publications

Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis

Polymorphic Variants in NR1I3 and UGT2B7 Predict Taxane Neurotoxicity and Have Prognostic Relevance in Patients With Breast Cancer: A Case‐Control Study

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