Impact of genetic factors on platinum-induced gastrointestinal toxicity

Zheng, Yi; Deng, Zheng; Tang, Mimi; Xiao, Di; Cai, Pei

doi:10.1016/j.mrrev.2020.108324

Cited by 5 publications

(4 citation statements)

References 163 publications

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“…The interindividual differences in platinum-related GI toxicity are associated with genetic factors involved in platinum transport, metabolism, detoxification, DNA repair, cell cycle control, and apoptotic pathways. Sample size, ethnicity, design, treatment schedule, dosing, endpoint definition, and assessment of GI toxicity add complications to the interpretation of PGx-related ADRs [133].…”

Section: Cancermentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug–drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

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Section: Cancermentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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“…Its association with various cancer types, including skin ( 28 ), cervical ( 29 ), and lung cancers ( 30 ), underscores its potential as a therapeutic target across diverse malignancies. Prior research has highlighted the critical role of genetic variations, particularly single nucleotide polymorphisms (SNPs) within the CDC25C family, as key factors influencing the survival and chemotherapy response in advanced NSCLC patients ( 31 ). Moreover, the selective splicing of the CDC25C gene has been identified as a crucial mechanism controlling the progression of the mitotic cell cycle and the development of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Regulatory role of the miR-142-3p/CDC25C axis in modulating autophagy in non-small cell lung cancer

Meng,

Song,

Cong

et al. 2024

Transl Lung Cancer Res

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Background With its diverse genetic foundation and heterogeneous nature, non-small cell lung cancer (NSCLC) needs a better comprehension of prognostic evaluation and efficient treatment targeting. Methods Bioinformatics analysis was performed of The Cancer Genome Atlas (TCGA)-NSCLC and GSE68571 dataset. Overlapping differentially expressed genes (DEGs) were used for functional enrichment analysis and constructing the protein-protein interaction (PPI) network. In addition, key prognostic genes were identified through prognostic risk models, and their expression levels were verified. The phenotypic effects of cell division cycle 25C ( CDC25C ) regulation on NSCLC cell lines were assessed by in vitro experiments using various techniques such as flow cytometry, Transwell, and colony formation. Protein levels related to autophagy and apoptosis were assessed, specifically examining the impact of autophagy inhibition [3-methyladenine (3-MA)] and the miR-142-3p/ CDC25C axis on this regulatory system. Results CDC25C was identified as a key prognostic marker in NSCLC, showing high expression in tumor samples. In vitro experiments showed that CDC25C knockdown markedly reduced the capacity of cells to proliferate, migrate, invade, trigger apoptosis, and initiate cell cycle arrest. CDC25C and miR-142-3p displayed a reciprocal regulatory relationship. CDC25C reversed the inhibitory impacts of miR-142-3p on NSCLC cell cycle proliferation and progression. The synergy of miR-142-3p inhibition, CDC25C silencing, and 3-MA treatment was shown to regulate NSCLC cell processes including proliferation, apoptosis, and autophagy. Conclusions MiR-142-3p emerged as a key player in governing autophagy and apoptosis by directly targeting CDC25C expression. This emphasizes the pivotal role of the miR-142-3p/ CDC25C axis as a critical regulatory pathway in NSCLC.

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“…These side effects include neurotoxicity, nephrotoxicity, ototoxicity, and gastrointestinal toxicity. It is worth noting that approximately 80% of patients with epithelial ovarian cancer experience tumor recurrence and chemotherapy failure due to resistance to platinum-based drugs [ 12 , 13 , 14 ]. Additionally, Pt(II) regimens require intravenous injection for drug administration, as oral administration is ineffective and inconvenient for patients.…”

Section: Introductionmentioning

confidence: 99%

Current Status of Novel Multifunctional Targeted Pt(IV) Compounds and Their Reductive Release Properties

Xu,

Kong,

et al. 2024

Molecules

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Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.

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Impact of genetic factors on platinum-induced gastrointestinal toxicity

Cited by 5 publications

References 163 publications

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Regulatory role of the miR-142-3p/CDC25C axis in modulating autophagy in non-small cell lung cancer

Current Status of Novel Multifunctional Targeted Pt(IV) Compounds and Their Reductive Release Properties

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