Emerging roles of nucleotide metabolism in cancer development: progress and prospect

Ma, Jianchao; Zhong, Min; Xiong, Yubo; Gao, Zhi; Wu, Zhengxin; Liu, Yu; Hong, Xuehui

doi:10.18632/aging.202962

Cited by 43 publications

(63 citation statements)

References 88 publications

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“…Multiple metabolic processes are altered in tumorigenesis and cancer progression [ 68 , 72 , 73 ]. The increased demand for nitrogen is regarded as one of the important metabolic hallmarks of cancer cells reported by Pavlova and Thompson [ 74 ].…”

Section: Introductionmentioning

confidence: 99%

“…With continuous in-depth study of chemotherapy and cancers, our understanding of nucleotide metabolism in tumors has revealed their non-proliferative effects beyond their effects on cancer cell proliferation [ 8 ]. Dysregulated nucleotide metabolism has been found to alter the immune microenvironment and affect the host immune response [ 72 , 165 ]. Altered immune components in the TME indicate the potential application of immunotherapy, which is considered one of most promising approaches to precisely killing tumors and maintaining the immune microenvironment in the era of precision medicine.…”

Section: Introductionmentioning

confidence: 99%

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Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy

Gong

et al. 2022

J Hematol Oncol

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Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of nucleotide metabolism, our understanding of nucleotide metabolism in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness of nucleotide antimetabolites for enhancing immunotherapy. A growing body of evidence now supports the concept that targeting nucleotide metabolism can increase the antitumor immune response by (1) activating host immune systems via maintaining the concentrations of several important metabolites, such as adenosine and ATP, (2) promoting immunogenicity caused by increased mutability and genomic instability by disrupting the purine and pyrimidine pool, and (3) releasing nucleoside analogs via microbes to regulate immunity. Therapeutic approaches targeting nucleotide metabolism combined with immunotherapy have achieved exciting success in preclinical animal models. Here, we review how dysregulated nucleotide metabolism can promote tumor growth and interact with the host immune system, and we provide future insights into targeting nucleotide metabolism for immunotherapeutic treatment of various malignancies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy

Gong

et al. 2022

J Hematol Oncol

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“…Purines and pyrimidines participate in a wide range of biological processes, e.g., in cell proliferation [ 28 ]. Their abnormal metabolism may point to tumor development or progression [ 29 , 30 ]. Elevated levels of methylguanine, observed in the presented study, might be associated with enhanced nucleic acid turnover or their intensified methylation.…”

Section: Discussionmentioning

confidence: 99%

Pre- and Post-Resection Urine Metabolic Profiles of Bladder Cancer Patients: Results of Preliminary Studies on Time Series Metabolomics Analysis

Jacyna

Kordalewska

Artymowicz

et al. 2022

Cancers

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The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.

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“…However, nucleotide synthesis is a key cellular process, and the development of inhibitors is limited by side-effect toxicity, which could be alleviated by identifying and targeting regulatory mechanisms specific to tumor cells or to tissue types. Few organ-specific nucleotide metabolases in tumors have been discovered, and development of compounds targeting these enzymes hold great promise for patient treatment (Feng et al , 2020; Ma et al , 2021).…”

Section: Discussionmentioning

confidence: 99%

A metabolic map of the DNA damage response identifies PRDX1 in nuclear ROS scavenging and aspartate synthesis

Moretton

Kourtis

Calabrò

et al. 2022

Preprint

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While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be reported. Here, we investigate the metabolic enzymes and processes that are essential when cells are exposed to DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Subsequent analysis identified Peroxiredoxin 1, PRDX1, as fundamental for DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it is required to reduce DNA damage-induced nuclear reactive oxygen species. Moreover, PRDX1 regulates aspartate availability, which is required for the DNA damage-induced upregulation of de novo nucleotide synthesis. Loss of PRDX1 leads to an impairment in the clearance of DNA damage, accumulation of replicative stress and cell proliferation defects, thus revealing a crucial role for PRDX1 as a DNA damage surveillance factor.

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Emerging roles of nucleotide metabolism in cancer development: progress and prospect

Cited by 43 publications

References 88 publications

Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy

Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy

Pre- and Post-Resection Urine Metabolic Profiles of Bladder Cancer Patients: Results of Preliminary Studies on Time Series Metabolomics Analysis

A metabolic map of the DNA damage response identifies PRDX1 in nuclear ROS scavenging and aspartate synthesis

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