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Journal of Clinical Oncology : Official... Sep 2022To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
PURPOSE
To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
METHODS
An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022.
RESULTS
The search identified 19 studies informing the evidence base.
RECOMMENDATIONS
Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline and pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.
Topics: Adenosine Diphosphate; Antibodies, Monoclonal, Humanized; Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Class I Phosphatidylinositol 3-Kinases; Female; Fulvestrant; Humans; Immune Checkpoint Inhibitors; Ligands; Phosphatidylinositol 3-Kinases; Poly(ADP-ribose) Polymerase Inhibitors; Prospective Studies; Retrospective Studies; Ribose
PubMed: 35759724
DOI: 10.1200/JCO.22.01063 -
Frontiers in Genetics 2022infects millions and kills thousands of people annually the world over. With the emergence of artemisinin and/or multidrug resistant strains of the pathogen, it has...
infects millions and kills thousands of people annually the world over. With the emergence of artemisinin and/or multidrug resistant strains of the pathogen, it has become even more challenging to control and eliminate the disease. Multiomics studies of the parasite have started to provide a glimpse into the confounding genetics and mechanisms of artemisinin resistance and identified mutations in Kelch13 (K13) as a molecular marker of resistance. Over the years, thousands of genomes and transcriptomes of artemisinin-resistant/sensitive isolates have been documented, supplementing the search for new genes/pathways to target artemisinin-resistant isolates. This meta-analysis seeks to recap the genetic landscape and the transcriptional deregulation that demarcate artemisinin resistance in the field. To explore the genetic territory of artemisinin resistance, we use genomic single-nucleotide polymorphism (SNP) datasets from 2,517 isolates from 15 countries from the MalariaGEN Network (The Pf3K project, pilot data release 4, 2015) to dissect the prevalence, geographical distribution, and co-existing patterns of genetic markers associated with/enabling artemisinin resistance. We have identified several mutations which co-exist with the established markers of artemisinin resistance. Interestingly, K13-resistant parasites harbor α-ß hydrolase and putative HECT domain-containing protein genes with the maximum number of SNPs. We have also explored the multiple, publicly available transcriptomic datasets to identify genes from key biological pathways whose consistent deregulation may be contributing to the biology of resistant parasites. Surprisingly, glycolytic and pentose phosphate pathways were consistently downregulated in artemisinin-resistant parasites. Thus, this meta-analysis highlights the genetic and transcriptomic features of resistant parasites to propel further exploratory studies in the community to tackle artemisinin resistance.
PubMed: 35464842
DOI: 10.3389/fgene.2022.824483 -
Journal of Cancer Research and... Dec 2021To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a meta-analysis of published studies.
MATERIALS AND METHODS
Four randomized controlled trials (RCTs) were included in the meta-analysis. Data analysis was conducted in Review Manager 5.4.
RESULTS
The progression-free survival (PFS) of the patients with triple-negative (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.74-0.88; P < 0.00001) or hormone receptor-positive (HR 0.83; 95% CI 0.77-0.91; P < 0.0001) BRCA-mutated breast cancer was significantly extended in the containing PARPi therapy arm versus the chemotherapy arm. PFS of the patients who did not receive platinum-based therapy (HR 0.78; 95% CI 0.70-0.86; P < 0.0001) was significantly extended in the PARPi monotherapy arm versus the chemotherapy arm. The objective response rate of patients treated by PARPi monotherapy (risk ratio [RR] 2.51; 95% CI 1.81-3.47; P < 0.00001) was significantly higher than that of patients treated by chemotherapy. The incidence of thrombocytopenia in patients received PARPi combined therapy was obviously increased compared with chemotherapy group (RR 1.36; 95% CI 1.07-1.72; P = 0.01). PARPi monotherapy markedly increased the incidence of anemia (RR 5.83; 95% CI 2.64-12.88; P < 0.0001) versus chemotherapy. However, the risk of neutropenia (RR 0.48; 95% CI 0.29-0.81; P = 0.006) was reduced in the PARPi monotherapy arm. There were no statistical differences in other adverse events among these three groups.
CONCLUSIONS
PARPi combined therapy and monotherapy improved PFS of patients with BRCA-mutated breast cancer compared with standard chemotherapy, which was unrelated to type of BRCA mutation and status of hormone receptor. PARPi therapy has slightly higher hematological toxicity and better overall safety and tolerance.
PROSPERO REGISTRATION NUMBER
CRD42020204385.
Topics: Adenosine Diphosphate; Breast Neoplasms; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Ribose
PubMed: 35381738
DOI: 10.4103/jcrt.jcrt_2085_21 -
Journal of Gynecology Obstetrics and... Apr 2022This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer.
METHODS
Eligible studies were extracted from the electronic databases of PubMed, Web of Science, and EMBASE until 1 August 2019. The included studies investigated the correlation between PARP expression and clinical outcomes in patients with ovarian cancer. Clinical outcomes are overall survival (OS) and progression free survival (PFS). The clinical data of patients, such as clinicopathologic characteristics and survival, were analyzed. The language was limited to English, and studies conducted at the cellular level, animal studies, and non-original research were excluded. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for this meta-analysis.
RESULTS
A total of 9 eligible studies involving 1230 patients were included in our meta-analysis. Based on the analysis, higher PARP expression was correlated with worse overall survival [OS] (HR,1.64; 95% CI, 1.08-2.49; P = 0.020) in the univariate analysis, whereas results from multivariate analysis indicated that PARP overexpression wasn't statistically associated with worse OS (HR, 1.36; 95% CI, 0.98-1.90; P = 0.069). Moreover, the pooled results revealed that patients with PARP overexpression were not associated with worse histologic grade (OR,2.22; 95% CI, 0.98-5.02; P = 0.06).
CONCLUSION
PARP overexpression maybe associated with poor prognosis and survival in patients with ovarian cancer. The patients with PARP over expression were not tended to have a worse histologic grade. Findings require further validation.
Topics: Adenosine Diphosphate; Adenosine Diphosphate Ribose; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Prognosis; Ribose
PubMed: 35218983
DOI: 10.1016/j.jogoh.2022.102344 -
Experimental Dermatology May 2022The skin's ability to function optimally is affected by many diverse factors. Metabolomics has a great potential to improve our understanding of the underlying metabolic... (Review)
Review
The skin's ability to function optimally is affected by many diverse factors. Metabolomics has a great potential to improve our understanding of the underlying metabolic changes and the affected pathways. Therefore, the objective of this study was to review the current state of the literature and to perform further metabolic pathway analysis on the obtained data. The aim was to gain an overview of the metabolic changes under altered conditions and to identify common and different patterns as a function of the investigated factors. A cross-study comparison of the extracted studies from different databases identified 364 metabolites, whose concentrations were considerably altered by the following factor groups: irradiation, xenobiotics, ageing and skin diseases (mainly psoriasis). Using metabolic databases and pathway analysis tools, the individual metabolites were assigned to the corresponding metabolic pathways and the most strongly affected signalling pathways were identified. All factors induced oxidative stress. Thus, antioxidant defence systems, especially coenzyme Q (ageing) and the glutathione system (irradiation, ageing, xenobiotics), were impacted. Lipid metabolism was also impacted by all factors studied. The carnitine shuttle as part of β-oxidation was activated by all factor groups except ageing. Glycolysis, Krebs (TCA) cycle and purine metabolism were mainly affected by irradiation and xenobiotics. The pentose phosphate pathway was activated, and Krebs cycle was downregulated in response to oxidative stress. In summary, it can be ascertained that mainly energy metabolism, lipid metabolism, antioxidative defence and DNA repair systems were impacted by the factors studied.
Topics: Citric Acid Cycle; Energy Metabolism; Metabolomics; Pentose Phosphate Pathway; Xenobiotics
PubMed: 35030266
DOI: 10.1111/exd.14529 -
Archives of Gynecology and Obstetrics Aug 2021To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy... (Meta-Analysis)
Meta-Analysis Review
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.
PURPOSE
To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.
RESULTS
We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).
CONCLUSIONS
PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.
Topics: Adenosine Diphosphate; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Treatment Outcome
PubMed: 34021367
DOI: 10.1007/s00404-021-06070-2 -
Acta Paediatrica (Oslo, Norway : 1992) Aug 2021To systematically review human metabolomic studies investigating metabolic responses in septic neonates. (Review)
Review
AIM
To systematically review human metabolomic studies investigating metabolic responses in septic neonates.
METHODS
A systematic literature search was performed in the databases MEDLINE, EMBASE and Cochrane library up to the 1st of January 2021. We included studies that assessed neonatal sepsis and the following outcomes; (1) change in the metabolism compared to healthy neonates and/or (2) metabolomics compared to traditional diagnostic tools of neonatal sepsis. The screened abstracts were independently considered for eligibility by two researchers.
PROSPERO ID
CRD42020164454.
RESULTS
The search identified in total 762 articles. Fifteen articles were assessed for eligibility. Four studies were included, with totally 78 neonates. The studies used different diagnostic criteria and had between 1 and 16 sepsis cases. All studies with bacterial sepsis found alterations in the glucose and lactate metabolism, reflecting possible redistribution of glucose consumption from mitochondrial oxidative phosphorylation to the lactate and pentose phosphate pathway. We also found signs of increased oxidative stress and fatty acid oxidation in sepsis cases.
CONCLUSION
We found signs of metabolomic signatures in neonatal sepsis. This may lead to better understanding of sepsis pathophysiology and detection of new candidate biomarkers. Results should be validated in large-scale multicentre studies.
Topics: Anti-Bacterial Agents; Humans; Infant, Newborn; Metabolomics; Neonatal Sepsis; Research Design; Sepsis
PubMed: 33851423
DOI: 10.1111/apa.15874 -
Applied Microbiology and Biotechnology Aug 2020Ribose-5-phosphate isomerase (Rpi, EC 5.3.1.6) is widespread in microorganisms, animals, and plants. It has a pivotal role in the pentose phosphate pathway and...
Ribose-5-phosphate isomerase (Rpi, EC 5.3.1.6) is widespread in microorganisms, animals, and plants. It has a pivotal role in the pentose phosphate pathway and responsible for catalyzing the isomerization between D-ribulose 5-phosphate and D-ribose 5-phosphate. In recent years, Rpi has received considerable attention as a multipurpose biocatalyst for production of rare sugars, including D-allose, L-rhamnulose, L-lyxose, and L-tagatose. Besides, it has been thought of as a potential drug target in the treatment of trypanosomatid-caused diseases such as Chagas' disease, leishmaniasis, and human African trypanosomiasis. Despite increased research activities, up to now, no systematic review of Rpi has been published. To fill this gap, this paper provides detailed information about the enzymatic properties of various Rpis. Furthermore, structural features, catalytic mechanism, and molecular modifications of Rpis are summarized based on extensive crystal structure research. Additionally, the applications of Rpi in rare sugar production and the role of Rpi in trypanocidal drug design are reviewed. Key points • Fundamental properties of various ribose-5-phosphate isomerases (Rpis). • Differences in crystal structure and catalytic mechanism between RpiA and RpiB. • Application of Rpi as a rare sugar producer and a potential drug target.
Topics: Aldose-Ketose Isomerases; Animals; Binding Sites; Biocatalysis; Crystallography, X-Ray; Humans; Isomerism; Kinetics; Models, Molecular; Parasitic Diseases; Plants; Ribosemonophosphates
PubMed: 32533303
DOI: 10.1007/s00253-020-10735-4 -
Metabolomics : Official Journal of the... Mar 2018Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, a common industrial chemical which has extremely huge production worldwide, is ubiquitous in the environment. Human...
INTRODUCTION
Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, a common industrial chemical which has extremely huge production worldwide, is ubiquitous in the environment. Human have high risk of exposing to BPA and the health problems caused by BPA exposure have aroused public concern. However, the biomarkers for BPA exposure are lacking. As a rapidly developing subject, metabolomics has accumulated a large amount of valuable data in various fields. The secondary application of published metabolomics data could be a very promising field for generating novel biomarkers whilst further understanding of toxicity mechanisms.
OBJECTIVES
To summarize the published literature on the use of metabolomics as a tool to study BPA exposure and provide a systematic perspectives of current research on biomarkers screening of BPA exposure.
METHODS
We conducted a systematic search of MEDLINE (PubMed) up to the end of June 25, 2017 with the key term combinations of 'metabolomics', 'metabonomics', 'mass spectrometry', 'nuclear magnetic spectroscopy', 'metabolic profiling' and 'amino acid profile' combined with 'BPA exposure'. Additional articles were identified through searching the reference lists from included studies.
RESULTS
This systematic review included 15 articles. Intermediates of glycolysis, Krebs cycle, β oxidation of long chain fatty acids, pentose phosphate pathway, nucleoside metabolism, branched chain amino acid metabolism, aromatic amino acids metabolism, sulfur-containing amino acids metabolism were significantly changed after BPA exposure, suggesting BPA had a highly complex toxic effects on organism which was consistent with existing studies. The biomarkers most consistently associated with BPA exposure were lactate and choline.
CONCLUSION
Existing metabolomics studies of BPA exposure present heterogeneous findings regarding metabolite profile characteristics. We need more evidence from target metabolomics and epidemiological studies to further examine the reliability of these biomarkers which link to low, environmentally relevant, exposure of BPA in human body.
Topics: Benzhydryl Compounds; Biomarkers; Humans; Metabolomics; Phenols
PubMed: 30830327
DOI: 10.1007/s11306-018-1342-z -
Journal of Gastroenterology and... Jan 2019While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS.
METHODS
Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis.
RESULTS
Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D-xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia.
CONCLUSIONS
Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests.
Topics: Anemia; Autoantibodies; Body Height; Celiac Disease; Diagnosis, Differential; Dyspepsia; Endoscopy, Gastrointestinal; Humans; Intestinal Mucosa; Sprue, Tropical; Vomiting; Xylose
PubMed: 30069926
DOI: 10.1111/jgh.14403