Approaches for Identifying Novel Targets in Precision Medicine: Lessons from DNA Repair

Williams, Dean T.; Staples, Christopher J.

doi:10.1007/978-3-319-60733-7_1

Cited by 5 publications

(5 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthetic lethal interactions are utilized by these kinds of therapy to design personalized medicine which depends on the patient's molecular profiling and behavior of cancer cells. Several benefits of using patient profiling starting from the determination of drug resistance after relapse, could also help in adjusting the therapeutic dose [155]. Precision medicine is a new type of treatment that plays a critical role in selecting the most appropriate therapy at the suitable time, as it only succeeds in targeting the DNA repair pathway in cancer.…”

Section: Discussionmentioning

confidence: 99%

DNA Damage/Repair Management in Cancers

Alhmoud

Woolley

Moustafa

et al. 2020

Cancers

233

132

View full text Add to dashboard Cite

DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

DNA Damage/Repair Management in Cancers

Alhmoud

Woolley

Moustafa

et al. 2020

Cancers

233

132

View full text Add to dashboard Cite

show abstract

“…Inactivation of proteins involved in the DNA damage response process has been described in a number of age-dependent diseases, including cancer, as well as progeroid syndromes. Therefore, modulation of DNA repair signaling pathways directly, or through their epigenetic regulation, is one of the potential therapeutic strategies [ 747 , 1100 , 1101 ]. In particular, the brain is an organ with a high level of oxygen and energy consumption.…”

Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

View full text Add to dashboard Cite

Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

show abstract

“…In addition, there is still rise the survival rate of patients for adjustment in the formulation of treatment plans. Nowadays, more and more studies have found that the recurrence and metastasis of tumors are closely related to the DNA repair regulatory system related to drug resistance [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

The Diagnostic Value of DNA Repair Gene in Breast Cancer Recurrence and Metastasis

Yang

Hao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: DNA repair genes play a vital role in the treatment of many cancers, and DNA repair genes can be used in breast cancer recurrence and metastasis research. We found that the expression of DNA repair genes in breast cancer patients after recurrence and metastasis is abnormal, however, the clinical predictive significance of DNA repair genes is still elusive. Methods: The nested case-control method was used in patients with breast cancer recurrence and metastasis after surgery (n=109) and patients without recurrence and metastasis after surgery (n=109). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. Results: PARP1(OR=1.485, 95%CI:1.279~1.725, P<0.05), XRCC4(OR= 1.419, 95%CI:1.217~ 1.656, P<0.05) and ERCC1 (OR=1.181, 95%CI: 1.032~1.353, P<0.05) were risk factors for postoperative recurrence and metastasis of breast cancer. Therefore, we used the ROC curve to study the optimal critical values of PARP1, XRCC4, and ERCC1, combined with the comprehensive judgment of clinical experience, we can conclude that PARP1 (cutoff value = 6, Se = 75.23%, Sp = 79.82%), XRCC4 (cutoff value = 6, Se = 78.9%0, Se = 79.82%), ERCC1 (cutoff value = 3, Se = 89.91%, Sp = 47.71%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of recurrence and metastasis will increases (ORPARP1 = 14.941, 95% CIPARP1: 4.004~55.758, P <0.05; ORXRCC4 = 16.740, 95% CIXRCC4: 6.433 ~ 43.560, P <0.05; ORERCC1 = 5.285, 95% CIERCC1: 1.843 ~ 15.156, P <0.05). Due to PARP1, ERCC1 and XRCC4 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-ERCC1=0.317; rPAPR1-XRCC4=0.329; rERCC1-XRCC4=0.377). The combined diagnosis of the PARR1,ERCC1 and XRCC4 have greater predictive value for the risk of recurrence and metastasis of breast cancer(Se = 88.99%, Sp = 82.57%；OR = 50.914, 95% CI: 10.918, 237.417, P <0.05).Conclusions: The recurrence and metastasis of breast cancer are predictive after PARP1>6, XRCC4>6, and ERCC1>3. The combined diagnosis of the three indicators have greater predictive value for the risk of recurrence and metastasis of breast cancer.

show abstract

Approaches for Identifying Novel Targets in Precision Medicine: Lessons from DNA Repair

Cited by 5 publications

References 99 publications

DNA Damage/Repair Management in Cancers

DNA Damage/Repair Management in Cancers

Genome-Protecting Compounds as Potential Geroprotectors

The Diagnostic Value of DNA Repair Gene in Breast Cancer Recurrence and Metastasis

Contact Info

Product

Resources

About