{"title":"Focus on the molecular mechanisms of cisplatin resistance based on multi-omics approaches","authors":"Ping Yue, Bingjie Han and Yi Zhao","doi":"10.1039/D2MO00220E","DOIUrl":null,"url":null,"abstract":"<p >Cisplatin is commonly used in combination with other cytotoxic agents as a standard treatment regimen for a variety of solid tumors, such as lung, ovarian, testicular, and head and neck cancers. However, the effectiveness of cisplatin is accompanied by toxic side effects, for instance, nephrotoxicity and neurotoxicity. The response of tumors to cisplatin treatment involves multiple physiological processes, and the efficacy of chemotherapy is limited by the intrinsic and acquired resistance of tumor cells. Although enormous efforts have been made toward molecular mechanisms of cisplatin resistance, the development of omics provides new insights into the understanding of cisplatin resistance at genome, transcriptome, proteome, metabolome and epigenome levels. Mechanism studies using different omics approaches revealed the necessity of multi-omics applications, which provide information at different cellular function levels and expand our recognition of the peculiar genetic and phenotypic heterogeneity of cancer. The present work systematically describes the underlying mechanisms of cisplatin resistance in different tumor types using multi-omics approaches. In addition to the classical mechanisms such as enhanced drug efflux, increased DNA damage repair and changes in the cell cycle and apoptotic pathways, other changes like increased protein damage clearance, increased protein glycosylation, enhanced glycolytic process, dysregulation of the oxidative phosphorylation pathway, ferroptosis suppression and mRNA m6A methylation modification can also induce cisplatin resistance. Therefore, utilizing the integrated omics to identify key signaling pathways, target genes and biomarkers that regulate chemoresistance are essential for the development of new drugs or strategies to restore tumor sensitivity to cisplatin.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 4","pages":" 297-307"},"PeriodicalIF":3.0000,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular omics","FirstCategoryId":"99","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2023/mo/d2mo00220e","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 5
Abstract
Cisplatin is commonly used in combination with other cytotoxic agents as a standard treatment regimen for a variety of solid tumors, such as lung, ovarian, testicular, and head and neck cancers. However, the effectiveness of cisplatin is accompanied by toxic side effects, for instance, nephrotoxicity and neurotoxicity. The response of tumors to cisplatin treatment involves multiple physiological processes, and the efficacy of chemotherapy is limited by the intrinsic and acquired resistance of tumor cells. Although enormous efforts have been made toward molecular mechanisms of cisplatin resistance, the development of omics provides new insights into the understanding of cisplatin resistance at genome, transcriptome, proteome, metabolome and epigenome levels. Mechanism studies using different omics approaches revealed the necessity of multi-omics applications, which provide information at different cellular function levels and expand our recognition of the peculiar genetic and phenotypic heterogeneity of cancer. The present work systematically describes the underlying mechanisms of cisplatin resistance in different tumor types using multi-omics approaches. In addition to the classical mechanisms such as enhanced drug efflux, increased DNA damage repair and changes in the cell cycle and apoptotic pathways, other changes like increased protein damage clearance, increased protein glycosylation, enhanced glycolytic process, dysregulation of the oxidative phosphorylation pathway, ferroptosis suppression and mRNA m6A methylation modification can also induce cisplatin resistance. Therefore, utilizing the integrated omics to identify key signaling pathways, target genes and biomarkers that regulate chemoresistance are essential for the development of new drugs or strategies to restore tumor sensitivity to cisplatin.
Molecular omicsBiochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
5.40
自引率
3.40%
发文量
91
期刊介绍:
Molecular Omics publishes high-quality research from across the -omics sciences.
Topics include, but are not limited to:
-omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance
-omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets
-omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques
-studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field.
Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits.
Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.