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Journal of Clinical Oncology : Official... Sep 2022To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
PURPOSE
To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
METHODS
An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022.
RESULTS
The search identified 19 studies informing the evidence base.
RECOMMENDATIONS
Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline and pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.
Topics: Adenosine Diphosphate; Antibodies, Monoclonal, Humanized; Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Class I Phosphatidylinositol 3-Kinases; Female; Fulvestrant; Humans; Immune Checkpoint Inhibitors; Ligands; Phosphatidylinositol 3-Kinases; Poly(ADP-ribose) Polymerase Inhibitors; Prospective Studies; Retrospective Studies; Ribose
PubMed: 35759724
DOI: 10.1200/JCO.22.01063 -
Journal of Dietary Supplements 2021Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities and . There...
Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities and . There is growing commercial interest in the application of astaxanthin in nutraceuticals and cosmeceuticals, due to its purported photoprotective, DNA repair, antioxidant, and anti-inflammatory benefits. This systematic review therefore aimed to summarize current clinical evidence on the effects of astaxanthin supplementation on skin health. Using the following combinations of broad Major Exploded Subject Headings (MesH) terms or text words [astaxanthin OR AST OR ASX OR carotenoid OR xanthophyll] AND [skin OR derm*], a comprehensive search of PubMed, EMBASE, Medline, Clinicaltrials.gov, and Google Scholar databases found a total of eleven clinical studies. There were six randomized, placebo-controlled, double-blind trials, while the rest were prospective, open-label studies. In many of the randomized, controlled trials reviewed, AST supplementation improved skin texture, appearance (wrinkles), and moisture content at the end of the study period. AST also appeared to protect against UV-induced skin damage. No serious adverse events were reported in any of the studies. However, most available studies had a relatively small sample size and were conducted on healthy Japanese females. Many of the studies were also funded by commercial entities, with potential conflicts of interests. This was difficult to account for in our analyses. Overall, there is some clinical data to support the benefits of astaxanthin supplementation (in the range of 3 to 6 mg/d) on skin health, especially for photoaged skin.
Topics: Dietary Supplements; Female; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Skin; Xanthophylls
PubMed: 32202443
DOI: 10.1080/19390211.2020.1739187 -
The Journal of Clinical and Aesthetic... Jun 2023Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less...
Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less toxic compared to systemic therapies. This systematic review aims to inform dermatology providers of the risks and benefits of phototherapy, especially in patients at risk for malignancies. Ionizing energy from phototherapy results in DNA photolesions, namely of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Without adequate repair, these mutations increase the risk for carcinogenesis. Additionally, phototherapy can also indirectly cause DNA damage through the formation of reactive oxygen species (ROS), which damage of several structural and functional proteins and DNA. When choosing a phototherapy modality, it also important to take into consideration the side effect profiles associated with each modality. For instance, a 10-fold higher dose of NB-UVB is required to produce a similar amount of CPDs compared with BB-UVB. Patients who undergo UVA with psoralen (PUVA) can be susceptible to developing skin malignancies up to 25 years after receiving their last treatment. It would behoove providers to consider optimal radiation dosage given each patients' level of skin pigmentation and potential for photoadaptation. Additionally, there are measures have been proposed to minimize deleterious skin changes, such as a 42-degree Celsius heat treatment using a 308nm excimer laser prior to UVB phototherapy and low frequency, low intensity electromagnetic fields along with UVB. However, as performing routine skin exams, remain paramount in the prevention of phototherapy-induced neoplasia.
PubMed: 37361361
DOI: No ID Found -
Wiley Interdisciplinary Reviews. RNA Nov 2021In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding... (Review)
Review
In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA-dependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N-MTase activity of EZH2, protein arginine-MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
Topics: Animals; Gene Expression Regulation; Methylation; Protein Processing, Post-Translational; RNA Processing, Post-Transcriptional; RNA, Long Noncoding
PubMed: 33913612
DOI: 10.1002/wrna.1661 -
Biology of Reproduction Sep 2015Oocyte aging has a significant impact on reproductive outcomes both quantitatively and qualitatively. However, the molecular mechanisms underlying the age-related... (Meta-Analysis)
Meta-Analysis Review
Oocyte aging has a significant impact on reproductive outcomes both quantitatively and qualitatively. However, the molecular mechanisms underlying the age-related decline in reproductive success have not been fully addressed. BRCA is known to be involved in homologous DNA recombination and plays an essential role in double-strand DNA break repair. Given the growing body of laboratory and clinical evidence, we performed a systematic review on the current understanding of the role of DNA repair in human reproduction. We find that BRCA mutations negatively affect ovarian reserve based on convincing evidence from in vitro and in vivo results and prospective studies. Because decline in the function of the intact gene occurs at an earlier age, women with BRCA1 mutations exhibit accelerated ovarian aging, unlike those with BRCA2 mutations. However, because of the still robust function of the intact allele in younger women and because of the masking of most severe cases by prophylactic oophorectomy or cancer, it is less likely one would see an effect of BRCA mutations on fertility until later in reproductive age. The impact of BRCA2 mutations on reproductive function may be less visible because of the delayed decline in the function of normal BRCA2 allele. BRCA1 function and ataxia-telangiectasia-mutated (ATM)-mediated DNA repair may also be important in the pathogenesis of age-induced increase in aneuploidy. BRCA1 is required for meiotic spindle assembly, and cohesion function between sister chromatids is also regulated by ATM family member proteins. Taken together, these findings strongly suggest the implication of BRCA and DNA repair malfunction in ovarian aging.
Topics: Animals; BRCA1 Protein; BRCA2 Protein; DNA Repair; Female; Fertility; Genes, BRCA2; Humans; Infertility; Mice; Ovary
PubMed: 26224004
DOI: 10.1095/biolreprod.115.132290 -
Medical Oncology (Northwood, London,... Aug 2016C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an... (Review)
Review
C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an evolutionarily conserved and multifunctional protein that involves in controlling cellular proliferation and apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage and repair. The CSN is a highly conservative protein from yeast to human and interacts with the cullin-RING family of ubiquitin ligases so that it could be execute a process of removing NEDD8, a ubiquitin-like polypeptide (deneddylase activity). The role of Jab1/CSN5's multi-function has been proved as being oncogenic in nature, what is more, Jab1/CSN5 has been confirmed by much evidence that it participates in the carcinogenesis progression and is tightly associated with poor prognosis. However, the biologic implication of Jab1/CSN5 activity during the cancer's development is unclear. We performed a systematic literature review and assessment from PubMed and Medline databases in this article. Jab1/CSN5 is participate in a lot of biologic responses, including cell proliferation, apoptosis, cell cycle regulation, DNA metabolism, invasion, DNA damage and repair, and recurrence. It also promotes cell transformation and tumorigenesis. In this review, we mainly expound the progress in the function and research advances of Jab1/CSN5 and in untangling the Jab1/CSN5 signaling pathway. Based on these bases, its potential as a therapeutic target for cancer can play a greater role in future cancer treatment.
Topics: Animals; COP9 Signalosome Complex; Carcinogenesis; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Peptide Hydrolases; Signal Transduction
PubMed: 27412572
DOI: 10.1007/s12032-016-0805-1 -
Ageing Research Reviews Aug 2017Frailty is an emerging geriatric syndrome characterized by higher vulnerability to stressors, with an increased risk of adverse health outcomes such as mortality,... (Review)
Review
Frailty is an emerging geriatric syndrome characterized by higher vulnerability to stressors, with an increased risk of adverse health outcomes such as mortality, morbidity, disability, hospitalization, and institutionalization. Although it is generally recognized to have a biological basis, no particular biological trait has been consistently associated to frailty status so far. In this work, epidemiological studies evaluating association of frailty status with alterations at cellular level - namely oxidative stress, genomic instability and DNA damage and repair biomarkers -were revised and compared. A total of 25 studies fulfilled inclusion/exclusion criteria and, consequently, were included in the review. Variations of oxidative stress biomarkers were often associated to frailty status in older people. On the contrary, genomic instability seems not to be linked to frailty. The only study which addressed the possible relationship between DNA repair modulations and frailty status also failed in finding association. Despite the large number of cellular alterations known to be associated with frailty, studies on this issue are still very scarce and limited to some of the possible cellular targets. The established link between DNA repair, genomic instability, and age and age-related disorders, encourage deeper investigations on this line.
Topics: Aged; Biomarkers; DNA Repair; Epidemiologic Studies; Frail Elderly; Genomic Instability; Genomics; Humans; Institutionalization; Oxidative Stress; Phenotype
PubMed: 28487242
DOI: 10.1016/j.arr.2017.05.001 -
Scientific Reports Mar 2022DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological... (Meta-Analysis)
Meta-Analysis
DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity. We included 55 case-control studies that evaluated 12 different cancers using 10 different DNA repair assays. The pooled OR of cancer risk (all cancer types combined) was 2.92 (95% Confidence Interval (CI) 2.49, 3.43) for the lowest DNA repair. Lower DNA repair was associated with all studied cancer types, and pooled ORs (95% CI) ranged from 2.02 (1.43, 2.85) for skin cancer to 7.60 (3.26, 17.72) for liver cancer. All assays, except the homologous recombination repair assay, showed statistically significant associations with cancer. The effect size ranged from 1.90 (1.00, 3.60) for the etoposide-induced double-strand break assay to 5.06 (3.67, 6.99) for the γ-H2AX assay. The consistency and strength of the associations support the use of these phenotypic biomarkers; however large-scale prospective studies will be important for understanding their use related to age and screening initiation.
Topics: Case-Control Studies; DNA Repair; Humans; Phenotype; Prospective Studies; Skin Neoplasms
PubMed: 35233009
DOI: 10.1038/s41598-022-07256-7 -
The World Journal of Men's Health Jan 2022Male ageing is often associated with defective sperm DNA remodeling mechanisms that result in poorly packaged chromatin and a decreased ability to repair DNA strand...
PURPOSE
Male ageing is often associated with defective sperm DNA remodeling mechanisms that result in poorly packaged chromatin and a decreased ability to repair DNA strand breaks. However, the impact of advanced paternal age on DNA fragmentation remains inconclusive. The aim of the present systematic review was to investigate the impact of advancing paternal age (APA) on DNA fragmentation.
MATERIALS AND METHODS
We conducted a thorough search of listed publications in Scopus, PubMed, and EMBASE, in accordance with the PRISMA guidelines.
RESULTS
We identified 3,120 articles, of which nineteen were selected for qualitative analysis, resulting in a sample of 40,668 men. Of the 19 articles evaluating the impact of APA on DFI% (DNA fragmentation Index) included, 4 were on Normozoospermic and subfertile men, 3 on normozoospermic, Oligoasthenoteratozoospermic and Teratozoospermic, 6 on fertile and infertile men, 4 on just infertile men, and 2 evaluated a general population. Seventeen of the ninrnteen studies demonstrated APA's effect and impact on DFI%.
CONCLUSIONS
Although there was no universal definition for APA, the present review suggests that older age is associated with increased DFI. In elderly men with normal semen parameters, further studies should be performed to assess the clinical implications of DFI, as a conventional semen analysis can often fail to detect an etiology for infertility.
PubMed: 33987998
DOI: 10.5534/wjmh.200195 -
Photodermatology, Photoimmunology &... Nov 2020DNA damage is one of the main factors responsible for photoageing and is predominantly attributed to ultraviolet irradiation (UV-R). Photoprotection by conventional...
BACKGROUND
DNA damage is one of the main factors responsible for photoageing and is predominantly attributed to ultraviolet irradiation (UV-R). Photoprotection by conventional sunscreens is exclusively prophylactic, and of no value, once DNA damage has occurred. As a result, the demand for DNA repair mechanisms inhibiting, reversing or delaying the pathologic events in UV-exposed skin has sparked research on anti-photoageing and strategies to improve the effect of conventional sunscreens. This review provides an overview of recent developments in DNA repair enzymes used in sunscreens and their impact on photoageing.
METHODS
A systematic review of the literature, up to March 2019, was conducted using the electronic databases, PubMed and Web of Science. Quality assessment was carried out using the Newcastle-Ottawa scale (NOS) to ensure inclusion of adequate quality studies only (NOS > 5).
RESULTS
Out of the 352 publications, 52 were considered relevant to the key question and included in the present review. Two major enzymes were found to play a major role in DNA damage repair in sunscreens: photolyase and T4 endonuclease V. These enzymes are capable of identifying and removing UV-R-induced dimeric photoproducts. Clinical studies revealed that sunscreens with liposome-encapsulated types of photolyase and/or T4 endonuclease V can enhance these repair mechanisms.
CONCLUSION
There is a lack of randomized controlled trials demonstrating the efficacy of DNA repair enzymes on photoageing, or a superiority of sunscreens with DNA repair enzymes compared to conventional sunscreens. Further studies are mandatory to further reveal pathogenic factors of photoageing and possible therapeutic strategies against it.
Topics: Animals; DNA Damage; DNA Repair; Deoxyribodipyrimidine Photo-Lyase; Deoxyribonuclease (Pyrimidine Dimer); Humans; Skin Aging; Sunscreening Agents; Ultraviolet Rays; Viral Proteins
PubMed: 32772409
DOI: 10.1111/phpp.12597