Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach

Lodovichi, Samuele; Cervelli, Tiziana; Pellicioli, Achille; Galli, Alvaro

doi:10.3390/ijms21186684

Cited by 33 publications

(16 citation statements)

References 204 publications

(227 reference statements)

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“…Therefore, further studies need to be performed to determine how inhibition of DSB repair by HDACi treatment will affect cancer cells’ destiny in their native tumor microenvironment. However, the inhibition of DNA repair has proven to be highly effective in combined treatment according to numerous clinical trials [ 66 , 67 ], and the proposed combination with HDACi was aimed to decrease toxic side effects for cancer patients, increasing the effectiveness of genotoxic drugs and targeting only cancer cells.…”

Section: Discussionmentioning

confidence: 99%

HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts

Gnedina

Morshneva

Skvortsova

et al. 2022

IJMS

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Many cancer therapy strategies cause DNA damage leading to the death of tumor cells. The DNA damage response (DDR) modulators are considered as promising candidates for use in combination therapy to enhance the efficacy of DNA-damage-mediated cancer treatment. The inhibitors of histone deacetylases (HDACis) exhibit selective antiproliferative effects against transformed and tumor cells and could enhance tumor cell sensitivity to genotoxic agents, which is partly attributed to their ability to interfere with DDR. Using the comet assay and host-cell reactivation of transcription, as well as ɣH2AX staining, we have shown that sodium butyrate inhibited DNA double-strand break (DSB) repair of both endo- and exogenous DNA in transformed but not in normal cells. According to our data, the dysregulation of the key repair proteins, especially the phosphorylated Mre11 pool decrease, is the cause of DNA repair impairment in transformed cells. The inability of HDACis to obstruct DSB repair in normal cells shown in this work demonstrates the advantages of HDACis in combination therapy with genotoxic agents to selectively enhance their cytotoxic activity in cancer cells.

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Section: Discussionmentioning

confidence: 99%

HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts

Gnedina

Morshneva

Skvortsova

et al. 2022

IJMS

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“…Some new results have been made in the studies which explored the relationship between DNA repair-related genes and cancers. A past study suggested that gene alterations in DNA repair pathways promoted cancer aggressiveness and induced the resistance to DNA damage cancer treatments [25].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Prognosis-Associated DNA Repair Gene Signatures in Colorectal Cancer

Song¹,

Zhang²,

Chen³

et al. 2021

Preprint

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Colorectal cancer (CRC) is the third most common malignant tumor. DNA damage played a crucial role on tumorigenesis, and abnormal DNA repair pathways affected the occurrence and progress of CRC. In current study, we aimed to construct a DNA repair-related genes (DRG) signature to predict the overall survival (OS) of CRC patients. Differentially expressed DRGs (DE-DRGs) were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic gene signature was identified by univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated by utilizing Kaplan-Meier curves and Time-dependent receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA) was performed to explore the underlying biological processes and signaling pathways. Single sample gene set enrichment analysis (ssGSEA) was implemented to estimate the immune status between the different risk group. A total of 118 DE-DRGs were identified between 42 normal samples and 488 CRC samples in TCGA cohort, and 36 DE-DRGs were associated with OS in the univariate Cox regression. A 9 DE-DRGs (ESCO2, AXIN2, PLK1, CDC25C, IGF1, TREX2, ALKBH2, ESR1 and MC1R) signature was constructed to classify patients into high-risk and low-risk group. The risk score was an independent prognostic indicator for OS (HR>1, P<0.001). Genetic alterations analysis indicated that the 9 DE-DRGs in the signature were changed in 63 required samples (100%) and the major alteration was missense mutation. The function enrichment analysis indicated that RNAi effector complex, sensory perception of smell and olfactory receptor activity were the main biological processes. The high-risk group had higher immune cell infiltration levels than low-risk group. The 9 DE-DRGs signature was significantly associated with OS and provided a new insight for the diagnosis and treatment for CRC. The predictive ability of this model need be supported by further basic researches.

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“…Although this situation is more complex, the answer appears to be yes. For example, a major component of current work on chemotherapy has the goal of finding compounds that specifically inhibit cancer cell biochemistry while doing minimal damage to healthy cell biochemistry [ 27 , 28 , 29 , 30 , 31 , 32 ]. The target is often DNA repair or DNA replication because of the more rapid DNA replication of tumor cells [ 28 , 29 , 30 , 31 , 32 ].…”

Section: Phages and Phage Dna Packaging In Relation To Biomedicine: A...mentioning

confidence: 99%

A Perspective on Studies of Phage DNA Packaging Dynamics

Serwer

2022

IJMS

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The Special Issue “DNA Packaging Dynamics of Bacteriophages” is focused on an event that is among the physically simplest known events with biological character. Thus, phage DNA (and RNA) packaging is used as a relatively accessible model for physical analysis of all biological events. A similar perspective motivated early phage-directed work, which was a major contributor to early molecular biology. However, analysis of DNA packaging encounters the limitation that phages vary in difficulty of observing various aspects of their packaging. If a difficult-to-access aspect arises while using a well-studied phage, a counterstrategy is to (1) look for and use phages that provide a better access “window” and (2) integrate multi-phage-accessed information with the help of chemistry and physics. The assumption is that all phages are characterized by the same evolution-derived themes, although with variations. Universal principles will emerge from the themes. A spin-off of using this strategy is the isolation and characterization of the diverse phages needed for biomedicine. Below, I give examples in the areas of infectious disease, cancer, and neurodegenerative disease.

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Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach

Cited by 33 publications

References 204 publications

HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts

HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts

Identification and Validation of Prognosis-Associated DNA Repair Gene Signatures in Colorectal Cancer

A Perspective on Studies of Phage DNA Packaging Dynamics

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