المؤلفون: Jinling Ji, Ting Shi, Lei Yan, Kai Wang, Kun Jiang, Yuzhang Jiang, Shengnan Pan, Yabin Yu, Chang Li

المصدر: Frontiers in Oncology; 2024, p1-12, 12p

مصطلحات موضوعية: PLEURAL effusions, CARCINOEMBRYONIC antigen, MULTIPLE regression analysis, LOGISTIC regression analysis, LACTATE dehydrogenase, COPPER

مستخلص: Background: Malignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE. Methods: From July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram's performance, including calibration, discrimination, and clinical applicability. Results: Seven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients. Conclusion: This study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE. [ABSTRACT FROM AUTHOR]

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المؤلفون: Mengjie Yu, Wei Wen, Yue Wang, Xia Shan, Xin Yi, Wei Zhu, Jiye Aa, Guangji Wang

المصدر: Frontiers in Oncology; 2024, p01-17, 17p

مصطلحات موضوعية: MACHINE learning, METABOLOMICS, METABOLIC reprogramming, OXALATES, LACTATE dehydrogenase

مستخلص: Background: Metabolic reprogramming plays a significant role in the advancement of lung adenocarcinoma (LUAD), yet the precise metabolic changes remain incompletely understood. This study aims to uncover metabolic indicators associated with the progression of LUAD. Methods: A total of 1083 subjects were recruited, including 670 LUAD, 135 benign lung nodules (BLN) and 278 healthy controls (HC). Gas chromatographymass spectrometry (GC/MS) was used to identify and quantify plasma metabolites. Odds ratios (ORs) were calculated to determine LUAD risk factors, and machine learning algorithms were utilized to differentiate LUAD from BLN. Results: High levels of oxalate, glycolate, glycine, glyceric acid, aminomalonic acid, and creatinine were identified as risk factors for LUAD (adjusted ORs>1.2, P<0.03). Remarkably, oxalate emerged as a distinctive metabolic risk factor exhibiting a strong correlation with the progression of LUAD (adjusted OR=5.107, P<0.001; advanced-stage vs. early-stage). The Random Forest (RF) model demonstrated a high degree of efficacy in distinguishing between LUAD and BLN (accuracy = 1.00 and 0.73, F1-score= 1.00 and 0.79, and AUC = 1.00 and 0.76 in the training and validation sets, respectively). TCGA and GTEx gene expression data have shown that lactate dehydrogenase A (LDHA), a crucial enzyme involved in oxalate metabolism, is increasingly expressed in the progression of LUAD. High LDHA expression levels in LUAD patients are also linked to poor prognoses (HR=1.66, 95% CI=1.34-2.07, P<0.001). [ABSTRACT FROM AUTHOR]

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المؤلفون: Jiaxin Wang, Huaijuan Guo, Jingjing Yang, Jingxian Mao, Ying Wang, Xuebing Yan, Hong Guo

المصدر: Frontiers in Oncology; 2024, p01-11, 11p

مصطلحات موضوعية: IMMUNE checkpoint inhibitors, CANCER patients, PROGNOSTIC models, IPILIMUMAB, NEUTROPHIL lymphocyte ratio, LACTATE dehydrogenase

مستخلص: Objective: Increasing studies have highlighted the potential utility of noninvasive prognostic biomarkers in advanced lung cancer patients receiving immune checkpoint inhibitor (ICI) based anti-cancer therapies. Here, a novel prognostic predictor named as C-PLAN integrating C-reactive protein (CRP), Performance status (PS), Lactate dehydrogenase (LDH), Albumin (ALB), and derived Neutrophil-to-lymphocyte ratio (dNLR) was identified and validated in a single-center retrospective cohort. Methods: The clinical data of 192 ICI-treated lung cancer patients was retrospectively analyzed. The pretreatment levels of CRP, PS, LDH, ALB and dNLR were scored respectively and then their scores were added up to form C- PLAN index. The correlation of C-PLAN index with the progression-free survival (PFS) or overall survival (OS) was analyzed by a Kaplan-Meier model. The multivariate analysis was used to identify whether C-PLAN index was an independent prognostic predictor. Results: A total of 88 and 104 patients were included in the low and high C-PLAN index group respectively. High C-PLAN index was significantly correlated with worse PFS and OS in ICI-treated lung cancer patients (both p<0.001). The multivariate analysis revealed high C-PLAN index was an independent unfavorable factor affecting PFS (hazard ratio (HR)=1.821; 95%confidence interval (CI)=1.291-2.568) and OS (HR=2.058, 95%CI=1.431-2.959). The high C-PLAN index group had a significantly lower disease control rate than the low C-PLAN index group (p=0.024), while no significant difference was found for objective response rate (p=0.172). The subgroup analysis based on clinical features (pathological type, therapy strategy, TNM stage and age) confirmed the prognostic value of C-PLAN index, except for patients receiving ICI monotherapy or with age ranging from 18 to 65 years old. Finally, a nomogram was constructed based on C-PLAN index, age, gender, TNM stage and smoking status, which could predict well the 1-, 2- and 3-year survival of ICI-treated lung cancer patients. Conclusion: The C-PLAN index has great potential to be utilized as a noninvasive, inexpensive and reliable prognostic predictor for advanced lung cancer patients receiving ICI-based anti-cancer therapies. [ABSTRACT FROM AUTHOR]

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المؤلفون: Dawe, David E., Rittberg, Rebekah, Syed, Iqra, Shanahan, Mary Kate, Moldaver, Daniel, Bucher, Oliver, Galloway, Katie, Reynolds, Kayla, Paul, James T., Harlos, Craig, Kim, Julian O., Banerji, Shantanu

المصدر: Frontiers in Oncology; 2023, p1-13, 13p

مصطلحات موضوعية: OVERALL survival, LUNG cancer, PROPORTIONAL hazards models, LACTATE dehydrogenase, PROGNOSIS

مصطلحات جغرافية: MANITOBA

مستخلص: Background: Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential. Objective: This real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada. Methods: A retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6−24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models. Results: Over the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1 −2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3−4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival. Conclusion: Survival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI. [ABSTRACT FROM AUTHOR]

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المؤلفون: Nübel, Charlotte, Amaral, Teresa, Leiter, Ulrike, Flatz, Lukas, Forschner, Andrea

المصدر: Frontiers in Oncology; 2023, p1-12, 12p

مصطلحات موضوعية: IPILIMUMAB, IMMUNE checkpoint inhibitors, ADVERSE health care events, MELANOMA, NIVOLUMAB, LACTATE dehydrogenase

مستخلص: Introduction: Combined immune checkpoint inhibition (ICI) with ipilimumab and nivolumab is a widely used treatment regimen for metastatic melanoma with non-resectable metastases. Nevertheless, the standard dose of ipilimumab 3 mg/kg bw and nivolumab 1 mg/kg bw is associated with a high rate of treatmentrelated adverse events (trAEs) (59% grade 3-4). In the CheckMate 511 study, it could be shown that flipped dosing with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw resulted in a significant reduction of trAE. Methods: We have also used this regimen in the clinical setting and report the trAE, progression-free survival, and overall survival for 79 patients with metastatic melanoma who started combined ICI in the flipped dosing between March 2019 and April 2020. Results: in total, 40 patients started first-line, 50% of whom had an elevated lactate dehydrogenase level at baseline. The disease control rate of these patients was 50%. The 2-year overall survival rate 67%. Moreover, 33% of the patients suffered grade 3 or 4 treatment related adverse events. Discussion: The results of our study correspond very well to the results of the CheckMate 511 study (2-year OS: 65%, grade 3-4 immune-related side effects: 35%). Combined ICI with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw seems to be an equally effective but better-tolerated therapy regimen for metastasized melanoma patients, also in a real-world cohort. [ABSTRACT FROM AUTHOR]

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المؤلفون: Sang Eun Yoon, Sujin Park, Junhun Cho, Kyung Ju Ryu, Booma Yandava, Sewon Lee, Seok Jin Kim, Won Seog Kim

المصدر: Frontiers in Oncology; 2023, p1-11, 11p

مصطلحات موضوعية: DIFFUSE large B-cell lymphomas, DIAGNOSIS, TUMOR microenvironment, LACTATE dehydrogenase

مستخلص: Introduction: Soluble MHC class I-related chain A (sMICA) and B (sMICB) play a critical role tumor evolution and poor prognosis through an immune evasion mechanism. Thus, this study determines the interaction between sMICA/sMICB and the tumor immune environment in newly diagnosed diffuse large B-cell lymphoma (ND-DLBCL). Methods: We analyzed sMICA/sMICB, cytokine in serum, and macrophage polarization analysis in tissue samples before the first chemotherapy administration. This research was performed to investigate the correlation between sMICA/sMICB expression and treatment outcomes as well as their influence on the immune system within ND-DLBCL. Results: Of the 262 patients, 47.3% (n = 124) presented stage III or IV at diagnosis and 50.8% (n = 133) had a high International Prognostic Index (IPI ≥ 3). The patients with high (p = 0.034 and 0.004), elevated lactate dehydrogenase (p = 0.002 and 0.030), advanced stage (p = 0.003 and 0.012), and higher IPI risk (p = 0.009, and 0.032) correlated with the detection of sMICA or sMICB. The median progression-free survival (PFS) of patients with sMICA (p = 0.006) or sMICB (p =0.032) was inferior. Among the patients with advanced-stage or high IPI, those with sMICA or sMICB presented an inferior PFS and OS compared to those without. TNF-a, a pro-inflammatory cytokine, showed statistical significance with detected sMICA (p = 0.035) or sMICB (p = 0.044). Among anti-inflammatory cytokines, IL-1RA (P-value = 0.013) and IL-10 (p = 0.005) were associated with detecting sMICB, but not sMICA. In tissue samples, sMICA or sMICB detection did not correlate with the CD68/CD163 ratio. Discussion: Conclusively, the identification of sMICA/sMICB presented unfavorable immunochemotherapy outcomes, and it was assumed that sMICA or sMICB and various cytokines interact, but the relationship with macrophage differentiation is unclear. Therefore, further research is needed to determine the relationship between sMICA/sMICB and tumor microenvironment in DLBCL. [ABSTRACT FROM AUTHOR]

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المؤلفون: Jinjin Chen, Xiaoyue Zou

المصدر: Frontiers in Oncology; 2023, p1-10, 10p

مصطلحات موضوعية: LACTATE dehydrogenase, STOMACH cancer, CANCER prognosis, PROGRESSION-free survival, MEDICAL databases

مستخلص: Background: The prognostic significance of lactate dehydrogenase (LDH) and its impact on the outcomes of gastric cancer (GC) is still unclear. We assessed the link between the levels of LDH and the overall survival (OS) and disease-free survival (DFS) in GC patients. Methods: A comprehensive search (both electronic and manual) was carried out in PubMed via MEDLINE, Web of Science (WoS), Experta Medical Database (Embase), and CENTRAL (Cochrane Library) databases for citations that evaluated the strength of association between LDH cut-off levels and OS and/or DFS in GC. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and heterogeneity was assessed. Results: Eighteen studies with 5328 patientswere included in our review. The overall pooled HR for OS was 1.48 (95% CI: 1.22-1.80) with high heterogeneity (I2 = 86%). Subgroup analyses showed that the link between LDH and OS was more prominent in Caucasian (HR 1.50 95% CI [0.80, 2.81], p=0.21) than in Asian cohorts (HR, 1.51 95% CI [1.21, 1.87], p=0.002). No significant overall association between LDH and OS (HR = 1.12, 95% CI: 0.76-1.65, p = 0.58) was found. Similar subgroup analyses results were reported for the association between LDH and DFS. Conclusion: In patients with GC, elevated LDH levels may correlate with worse OS and DFS, but the association is not significant. LDH is a significant predictor of OS but not of DFS. Further studies with larger sample sizes and more standardized criteria for defining elevated LDH levels are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

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المؤلفون: Xiaoyu Wei, Yumeng Chai, Zhouyue Li, Xuanyan Che, Yong Zhang, Zhongbao Zhou, Xiang Wang

المصدر: Frontiers in Oncology; 2023, p1-8, 8p

مصطلحات موضوعية: LACTATE dehydrogenase, BLADDER cancer, CANCER patients, PROGNOSIS, OVERALL survival

مستخلص: Background: A growing number of studies have considered serum lactate dehydrogenase (LDH) as an indicator of bladder cancer (BC) prognosis. However, a meta-analysis of the serum LDH's influence on BC prognosis is still missing. Methods: PubMed, EMBASE, Web of Science and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between high-LDH and low-LDH patients. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3) for overall survival (OS) in patients with BC. Results: Six studies involving 2,182 patients were selected according to predefined eligibility criteria. The results showed that serum LDH level was significantly associated with OS (HR = 1.86, 95%CI = 1.54-2.25, p<0.0001) in BC. Sensitivity analysis showed the stability of the results. Subgroup analysis revealed that the levels of serum LDH had a significant impact on the OS of BC patients among different groups including publication time, research country, sample size, tumor stage, LDH cut-off value, therapy and follow-up time (all HR>1 and p<0.05), revealing that the ability of serum LDH is not affected by other factors. Conclusion: Our findings indicated that a high level of serum LDH was associated with inferior OS in patients with BC. However, caution must be taken before recommendations are given because this interpretation is based upon very few clinical studies and a small sample. [ABSTRACT FROM AUTHOR]

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المؤلفون: Huohuan Tian, Guo Li, Wang Hou, Jing Jin, Chengdi Wang, Pengwei Ren, Haoyu Wang, Jie Wang, Weimin Li, Dan Liu

المصدر: Frontiers in Oncology; 2023, p1-11, 11p

مصطلحات موضوعية: SMALL cell lung cancer, OVERALL survival, RECEIVER operating characteristic curves, LACTATE dehydrogenase, RANKING (Statistics)

مستخلص: Objective: Various studies have investigated the predictive significance of numerous peripheral blood biomarkers in patients with small cell lung cancer (SCLC). However, their predictive values have not been validated. This study assessed and evaluated the ability of common nutritional or inflammatory indicators to predict overall survival (OS) in patients with SCLC who received first-line chemotherapy. Methods: Between January 2008 and July 2019, 560 patients with SCLC were enrolled at the Sichuan University West China Hospital. Eleven nutritional or inflammatory indices obtained before chemotherapy were evaluated. The cutoff values of continuous peripheral blood indices were confirmed through maximally selected rank statistics. The relationship of peripheral blood indices with OS was investigated through univariate and multivariate Cox regression analyses. Harrell's concordance (C-index) and time-dependent receiver operating characteristic curve were used to evaluate the performance of these indices. Results: A total of 560 patients with SCLC were enrolled in the study. All the patients received first-line chemotherapy. In the univariate Cox analysis, all indices, except the Naples score, were related to OS. In the multivariate analysis, albumin-globulin ratio was an independent factor linked with prognosis. All indices exhibited poor performance in OS prediction, with the area under the curve ranging from 0.500 to 0.700. The lactic dehydrogenase (LDH) and prognostic nutritional index (PNI) were comparatively superior predictors with C-index of 0.568 and 0.550, respectively. The LDH showed incremental predictive values, whereas the PNI showed diminishing values as survival time prolonged, especially for men or smokers. The LDH with highest sensitivity (0.646) and advanced lung cancer inflammation index (ALI) with highest specificity (0.952) were conducive to identifying death and survival at different time points. Conclusion: Common inflammatory or nutritional biomarkers are only marginally useful in predicting outcomes in patients with SCLC receiving firstline chemotherapy. Among them, LDH, PNI, and ALI are relatively promising biomarkers for prognosis evaluation. [ABSTRACT FROM AUTHOR]

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المؤلفون: Garbarino, Ombretta, Valenti, Giulia Elda, Monteleone, Lorenzo, Pietra, Gabriella, Mingari, Maria Cristina, Benzi, Andrea, Bruzzone, Santina, Ravera, Silvia, Leardi, Riccardo, Farinini, Emanuele, Vernazza, Stefania, Grottoli, Melania, Marengo, Barbara, Domenicotti, Cinzia

المصدر: Frontiers in Oncology; 2023, p1-20, 20p

مصطلحات موضوعية: SKIN cancer, NAD (Coenzyme), LACTATES, CANCER relapse, MELANOMA, PRINCIPAL components analysis, REACTIVE oxygen species, LACTATE dehydrogenase

مستخلص: Background: Malignant melanoma is the most lethal form of skin cancer which shows BRAF mutation in 50% of patients. In this context, the identification of BRAFV600E mutation led to the development of specific inhibitors like PLX4032. Nevertheless, although its initial success, its clinical efficacy is reduced after sixmonths of therapy leading to cancer relapse due to the onset of drug resistance. Therefore, investigating the mechanisms underlying PLX4032 resistance is fundamental to improve therapy efficacy. In this context, several models of PLX4032 resistance have been developed, but the discrepancy between in vitro and in vivo results often limits their clinical translation. Methods: The herein reported model has been realized by treating with PLX4032, for six months, patient-derived BRAF-mutated melanoma cells in order to obtain a reliable model of acquired PLX4032 resistance that could be predictive of patient's treatment responses. Metabolic analyses were performed by evaluating glucose consumption, ATP synthesis, oxygen consumption rate, P/O ratio, ATP/AMP ratio, lactate release, lactate dehydrogenase activity, NAD+/NADH ratio and pyruvate dehydrogenase activity in parental and drug resistant melanoma cells. The intracellular oxidative state was analyzed in terms of reactive oxygen species production, glutathione levels and NADPH/NADP+ ratio. In addition, a principal component analysis was conducted in order to identify the variables responsible for the acquisition of targeted therapy resistance. Results: Collectively, our results demonstrate, for the first time in patient-derived melanoma cells, that the rewiring of oxidative phosphorylation and the maintenance of pyruvate dehydrogenase activity and of high glutathione levels contribute to trigger the onset of PLX4032 resistance. Conclusion: Therefore, it is possible to hypothesize that inhibitors of glutathione biosynthesis and/or pyruvate dehydrogenase activity could be used in combination with PLX4032 to overcome drug resistance of BRAF-mutated melanoma patients. However, the identification of new adjuvant targets related to drug-induced metabolic reprogramming could be crucial to counteract the failure of targeted therapy in metastatic melanoma. [ABSTRACT FROM AUTHOR]

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