Glutathione S-Transferase Gene Polymorphisms are Associated with an Improved Treatment Response to Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

Wang, Hongyan; Gao, Xuehan; Zhang, Xiaolin; Gong, Wenjian; Peng, Ziheng; Wang, Bingshuang; Wang, Li; Chang, Saishuo; Ma, Pelosi; Wang, Shijie

doi:10.12659/msm.912373

Cited by 24 publications

(12 citation statements)

References 23 publications

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“…Our results are in concordance with others and indicate that deletions in GST genes are relatively common in different populations (23,7% to 51,6% for GSTM1 and 4,25% to 46,8% for GSTT1 ) [12]. According to the function of GSST1 and GSTM1 in the detoxification of exogenous compounds, the individuals carrying deletions have an increased risk for several cancers (colorectal and chronic myeloid leukemia) and toxicities related to medications [35–39]. Some of the toxicity reactions are secondary to a combination of deletions in GSST1 and GSTM1 genes.…”

Section: Discussionsupporting

confidence: 91%

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

et al. 2019

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Background: Copy Number variation (CNVs) in genes related to drug absorption, distribution, metabolism and excretion (ADME) are relevant in the interindividual variability of drug response. Studies of the CNVs in ADME genes in Latin America population are lacking. The objective of the study was to identify the genetic variability of CNVs in CYP-450 and GST genes in a subgroup of individuals of Colombian origin. Methods: Genomic DNA was isolated from 123 healthy individuals from a Colombian population. Multiplex Ligation-Dependent Probe Amplification (MLPA) was performed for the identification of CNVs in 40 genomic regions of 11 CYP-450 and 3 GST genes. The genetic variability, allelic and genotypic frequencies were analyzed. Results: We found that 13 out of 14 genes had CNVs: 5 (35.7%) exhibited deletions and duplications, while 8 (57.1%) presented either deletions or duplications.. 33.3% of individuals carried deletions and duplications while 49.6% had a unique type of CNV (deletion or duplication). The allelic frequencies of the CYP and GST genes were 0 to 47.6% (allele null), 0 to 17.5% (duplicated alleles) and 37 to 100% (normal alleles). Conclusions: Our results describe, for the first time, the genomic profile of CNVs in a subgroup of Colombian population in GST and CYP-450 genes. GST genes indicated greater genetic variability than CYP-450 genes. The data obtained contributes to the knowledge of genetic profiles in Latin American subgroups. Although the clinical relevance of CNVs has not been fully established, it is a valuable source of pharmacogenetic variability data with potential involvement in the response to medications.

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Section: Discussionsupporting

confidence: 91%

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

et al. 2019

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“…In all four statistical contrasts the Glutathione-mediated detoxification pathways were reported, which suggests a pronounced rs4845604 genotype effect irrespective of other cellular responses. The glutathione S-transferases (GSTs) comprise a family of detoxification enzymes that protect cells from intracellular reactive oxygen species [ 51 ], and GST genetic variability has been associated with susceptibility to a variety of toxins and an increase in certain cancers [ 52 , 53 ]. How the RORγt rs4845604 variant could regulate these enzymes is currently unknown, but the ROR family have been observed to regulate several enzymes involved in the metabolism of both synthetic and endogenous xenobiotic molecules [ 1 ], so a variant associated detoxification effect is biologically plausible.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic effects of rs4845604, an IBD and allergy-associated RORC variant, in stimulated ex vivo CD4+ T cells

Wilson

Franco

et al. 2021

PLoS ONE

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RORγt is an isoform of RORC, preferentially expressed in Th17 cells, that functions as a critical regulator of type 3 immunity. As murine Th17-driven inflammatory disease models were greatly diminished in RORC knock-out mice, this receptor was prioritised as an attractive therapeutic target for the treatment of several autoimmune diseases. Human genetic studies indicate a significant contributory role for RORC in several human disease conditions. Furthermore, genome-wide association studies (GWAS) report a significant association between inflammatory bowel disease (IBD) and the RORC regulatory variant rs4845604. To investigate if the rs4845604 variant may affect CD4+ T cell differentiation events, naïve CD4+ T cells were isolated from eighteen healthy subjects homozygous for the rs4845604 minor (A) or major (G) allele). Isolated cells from each subject were differentiated into distinct T cell lineages by culturing in either T cell maintenance medium or Th17 driving medium conditions for six days in the presence of an RORC inverse agonist (to prevent constitutive receptor activity) or an inactive diastereomer (control). Our proof of concept study indicated that genotype had no significant effect on the mean number of naïve CD4 T cells isolated, nor the frequency of Th1-like and Th17-like cells following six days of culture in any of the four culture conditions. Analysis of the derived RNA-seq count data identified genotype-driven transcriptional effects in each of the four culture conditions. Subsequent pathway enrichment analysis of these profiles reported perturbation of metabolic signalling networks, with the potential to affect the cellular detoxification response. This investigation reveals that rs4845604 genotype is associated with transcriptional effects in CD4+ T cells that may perturb immune and metabolic pathways. Most significantly, the rs4845604 GG, IBD risk associated, genotype may be associated with a differential detoxification response. This observation justifies further investigation in a larger cohort of both healthy and IBD-affected individuals.

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“…On the other hand, a positive correlation was observed between the level of the type GSTπ protein and cancer drug-resistance in variable neoplastic diseases [43][44][45][46]. At the gene level, there is a relationship between the GST gene polymorphism and tumor incidence [47] and the efficiency of chemotherapy [48,49].…”

Section: Drug Detoxificationmentioning

confidence: 99%

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

et al. 2021

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Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

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Glutathione S-Transferase Gene Polymorphisms are Associated with an Improved Treatment Response to Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

Cited by 24 publications

References 23 publications

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

Transcriptomic effects of rs4845604, an IBD and allergy-associated RORC variant, in stimulated ex vivo CD4+ T cells

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

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