Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Kciuk, Mateusz; Gielecińska, Adrianna; Mujwar, Somdutt; Kontek, Renata

doi:10.3390/ijms23073555

Cited by 15 publications

(6 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given their recent clinical successes in HGSOC, PARP inhibitors may be a lucrative class of drugs to test in combination with agents targeting amplified driver oncogenes. Indeed, pre-clinical evidence suggests cell cycle blockade and PARP inhibition may be synergistic [ 31 , 76 ]. Finally, inhibition of certain amplified therapeutic targets may also render the cancer more vulnerable to immunotherapy approaches.…”

Section: Perspectives and Future Researchmentioning

confidence: 99%

Amplified therapeutic targets in high-grade serous ovarian carcinoma – a review of the literature with quantitative appraisal

Talbot

Aboagye

2023

Cancer Gene Ther

View full text Add to dashboard Cite

High-grade serous ovarian carcinoma is a unique cancer characterised by universal TP53 mutations and widespread copy number alterations. These copy number alterations include deletion of tumour suppressors and amplification of driver oncogenes. Given their key oncogenic roles, amplified driver genes are often proposed as therapeutic targets. For example, development of anti-HER2 agents has been clinically successful in treatment of ERBB2-amplified tumours. A wide scope of preclinical work has since investigated numerous amplified genes as potential therapeutic targets in high-grade serous ovarian carcinoma. However, variable experimental procedures (e.g., choice of cell lines), ambiguous phenotypes or lack of validation hinders further clinical translation of many targets. In this review, we collate the genes proposed to be amplified therapeutic targets in high-grade serous ovarian carcinoma, and quantitatively appraise the evidence in support of each candidate gene. Forty-four genes are found to have evidence as amplified therapeutic targets; the five highest scoring genes are CCNE1, PAX8, URI1, PRKCI and FAL1. This review generates an up-to-date list of amplified therapeutic target candidates for further development and proposes comprehensive criteria to assist amplified therapeutic target discovery in the future.

show abstract

Section: Perspectives and Future Researchmentioning

confidence: 99%

Amplified therapeutic targets in high-grade serous ovarian carcinoma – a review of the literature with quantitative appraisal

Talbot

Aboagye

2023

Cancer Gene Ther

View full text Add to dashboard Cite

show abstract

“…The isomeric smiles for each of the concerned ligand was obtained from Pubchem database which was further utilized for the two-dimensional structure drawing of the ligands. [42][43][44][45][46][47] These two-dimensional structures were further undergone for the energy minimization step to save them in the energy minimized stable three-dimensional conformation required to perform docking based computational screening. Docking results were tabulated in Table 2 and the detailed information related to the utilized ligand library is provided as supplementary material in Table s1.…”

Section: Ligand Library Preparationmentioning

confidence: 99%

“…Thus, with intent to identify the most potent lead compound present in the above said plant by the computational screening of the chemical library against the shortlisted therapeutic targets associated with the progression of ulcerative colitis. The isomeric smiles for each of the concerned ligand was obtained from Pubchem database which was further utilized for the two‐dimensional structure drawing of the ligands [42–47] . These two‐dimensional structures were further undergone for the energy minimization step to save them in the energy minimized stable three‐dimensional conformation required to perform docking based computational screening.…”

Section: Introductionmentioning

confidence: 99%

A Network Pharmacology Study of the Active Components of Fufang Huangbai Ye for the Treatment of Ulcerative Colitis

Ke,

Yang,

Jiang

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

Computational study of the chemical constituents of the traditional Chinese medicinal plant HuangBai against therapeutic targets of ulcerative colitis by using network pharmacology with intent to identify potential candidates to develop novel therapy. Biomolecular proteins like IL1, IL6, JAK2, TNFα, TNFR1, etc. are found to be actively involved in the pathophysiological progression of ulcerative colitis. One of the most popular traditional Chinese medicinal plants, HuangBai, has been used since traditional times for the treatment of colon‐related issues, including inflammatory bowel disease. Thus, in the current research, an attempt has been made to identify the most potent chemical constituent of the concerned plant having therapeutic potential for the treatment of ulcerative colitis. Docking based screening of the prepared ligand library from the chemical constituent of the HuangBai plant against the therapeutic targets involved in the inflammatory reactions associated with ulcerative colitis. Docking results were further confirmed by performing in‐vitro cell line studies. Amurensin and melianone are found to be potent leads targeting inflammatory targets involved in the progression of ulcerative colitis and other inflammatory bowel diseases. Thus, it has been concluded that amurensin and melianone can be used for the development of novel therapeutics to benefit patients with ulcerative colitis.

show abstract

“…Another PIKK family kinase ATM (Tel1 in yeast) also contributes to the checkpoint control at G2/M. Transduction of the signal from ATM/ATR to downstream effector kinases involves BRCT-domain containing adaptor proteins 53BP1 and MDC1 and brings these regulators into proximity (Huen and Chen, 2008;Kciuk et al, 2022). CHK1 and CHK2 (yeast Chk1, Rad53) are the main effector kinases activated by ATM/ATR (Figure 3).…”

Section: Dna Damage Sensing Checkpoint Execution and G2 Arrest In Ver...mentioning

confidence: 99%

DNA damage checkpoint execution and the rules of its disengagement

Yam

Lim

Surana

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Chromosomes are susceptible to damage during their duplication and segregation or when exposed to genotoxic stresses. Left uncorrected, these lesions can result in genomic instability, leading to cells’ diminished fitness, unbridled proliferation or death. To prevent such fates, checkpoint controls transiently halt cell cycle progression to allow time for the implementation of corrective measures. Prominent among these is the DNA damage checkpoint which operates at G2/M transition to ensure that cells with damaged chromosomes do not enter the mitotic phase. The execution and maintenance of cell cycle arrest are essential aspects of G2/M checkpoint and have been studied in detail. Equally critical is cells’ ability to switch-off the checkpoint controls after a successful completion of corrective actions and to recommence cell cycle progression. Interestingly, when corrective measures fail, cells can mount an unusual cellular response, termed adaptation, where they escape checkpoint arrest and resume cell cycle progression with damaged chromosomes at the cost of genome instability or even death. Here, we discuss the DNA damage checkpoint, the mitotic networks it inhibits to prevent segregation of damaged chromosomes and the strategies cells employ to quench the checkpoint controls to override the G2/M arrest.

show abstract

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Cited by 15 publications

References 93 publications

Amplified therapeutic targets in high-grade serous ovarian carcinoma – a review of the literature with quantitative appraisal

Amplified therapeutic targets in high-grade serous ovarian carcinoma – a review of the literature with quantitative appraisal

A Network Pharmacology Study of the Active Components of Fufang Huangbai Ye for the Treatment of Ulcerative Colitis

DNA damage checkpoint execution and the rules of its disengagement

Contact Info

Product

Resources

About