Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7235 - 7235

Опубликована: Апрель 13, 2023

Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in development progression, epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, mRNA regulators (such miRNA mimics antagomiRs) can reverse these alterations. Therefore, are promising candidates for treatment. However, there is currently no effective epi-drug monotherapy breast cancer. Combining with conventional therapies has yielded positive outcomes may be strategy therapy. azacitidine, histone deacetylase vorinostat, have been used combination chemotherapy treat regulators, antagomiRs, alter the of specific genes involved development. mimics, miR-34, inhibit growth, while anti-miR-10b, metastasis. The epi-drugs target changes lead more options future.

Язык: Английский

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Hereditary Breast Cancer: Comprehensive Risk Assessment and Prevention Strategies

Genes, Год журнала: 2025, Номер 16(1), С. 82 - 82

Опубликована: Янв. 13, 2025

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP associated with cancer show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity penetrance disease. there are gaps translating how individual genomic variation affects phenotypic presentation. The expansion criteria for genetic testing increasing utilization comprehensive panels may enhance identification individuals linked to hereditary Individualized assessment could facilitate implementation personalized risk-reduction strategies these individuals. Preventive interventions encompass lifestyle modifications, chemoprevention, enhanced surveillance through imaging, risk-reducing surgeries. This review addresses current literature’s inconsistencies limitations, particularly regarding intensity preventive women genes. In addition, it synthesizes latest evidence on primary secondary prevention at high

Язык: Английский

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Genetically transitional disease: a new concept in genomic medicine

Trends in Genetics, Год журнала: 2022, Номер 39(2), С. 98 - 108

Опубликована: Дек. 21, 2022

Язык: Английский

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Theranostic biomarkers and PARP-inhibitors effectiveness in patients with non-BRCA associated homologous recombination deficient tumors: Still looking through a dirty glass window?

Cancer Treatment Reviews, Год журнала: 2023, Номер 121, С. 102650 - 102650

Опубликована: Окт. 31, 2023

Breast cancer susceptibility gene 1 (BRCA1) and breast 2 (BRCA2) deleterious variants were the first and, still today, main biomarkers of poly(ADP)ribose polymerase (PARP)-inhibitors (PARPis) benefit. The recent, increased, numbers individuals referred for counseling multigene panel testing, remarkable expansion approved PARPis, not restricted to BRCA1/BRCA2-Pathogenic Variants (PVs), produced a strong clinical need non-BRCA biomarkers. Significant limitations current testing assays exist. different approaches that identify causes Homologous Recombination Deficiency (HRD), such as germline somatic Repair (HRR) PVs, showing its consequences, genomic scars, or novel functional RAD51 foci are interchangeable, should be considered substitutes each other in practice guiding use PARPi non-BRCA, HRD-associated tumors. Today, deeper knowledge on significant relationship among all proteins involved HRR, limited BRCA, expands possibility successful HRD-PARPi synthetic lethality at same time, reinforces enhanced definition HRD predicting magnitude

Язык: Английский

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High-Grade Serous Ovarian Cancer—A Risk Factor Puzzle and Screening Fugitive

Biomedicines, Год журнала: 2024, Номер 12(1), С. 229 - 229

Опубликована: Янв. 19, 2024

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of female genital tract. Despite extensive studies and identification some precursor lesions like tubal intraepithelial (STIC) or deviated mutational status patients (BRCA germinal mutation), pathophysiology HGSOC existence particular risk factors still a puzzle. Moreover, lack screening programs results in delayed diagnosis, which accompanied by secondary chemo-resistance usually high recurrence rate after primary therapy. Therefore, there an urgent need to identify substantial for both predisposed low-risk populations women, as well create economically clinically justified program. This paper reviews classic novel methods diagnosis prediction, including serum biomarkers, liquid biopsy circulating cells DNA, epigenetic markers, exosomes, genomic proteomic biomarkers. The future complex approach should be devised based on these findings, general outcome such proposed discussed paper.

Язык: Английский

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Landscape of Multilocus Inherited Neoplasia Allele Syndrome in Mexican Population

JCO Global Oncology, Год журнала: 2025, Номер 11

Опубликована: Янв. 1, 2025

PURPOSE Hereditary cancer syndromes (HCS) explain 5%-10% of all cases. Patients with more than one germline pathogenic variant (GPV) result in a clinical syndrome known as multilocus inherited neoplasia allele (MINAS). In recent years, an increasing number MINAS cases have been reported. This study aims to identify the prevalence and determine effect two GPVs HCS on patients from Northern Mexico. METHODS (N = 2,282) were recruited four public oncology centers private institutions hereditary detection programs Nuevo León, México. A medical geneticist collected patient's data gave genetic counseling. detected using multigene panels detect GPVs; findings classified according American College Medical Genetics Genomics guidelines. The evaluated by their frequency combination. RESULTS We found 386 (16.9%) or variants 23 (5.9%) (all females). most frequent diagnosis was breast (BC) 20 (86.95%) cases, whereas 16 (69.56%) had triple-negative BC. 13 BRCA1 (56.52%) frequent, followed MUTYH five (21.73%). combinations BRCA1/CHEK2 , BRCA1/CDKN2A BRCA1/BRCA2 frequent. no atypical presentation cohort. CONCLUSION is first Mexican report largest Latin higher other populations (5.9%). tendency for additive phenotypical and, some combinations, modification age diagnosis.

Язык: Английский

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Personality traits of women with hereditary risk for breast/ovarian cancer versus obstetric history and cancer preventive behaviors

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 25, 2025

Abstract The aim of the study is to analyze relationship between personality traits women with hereditary predisposition breast/ovarian cancer and their obstetric history cancer-preventive behaviors. A total 357 women, participants ‘The National Program for Families With Genetic/Familial High Risk Cancer’, were included in study. Neo Five-Factor Inventory (NEO-FFI) a standardized original questionnaire designed purpose used. Breast ultrasound examination at younger age was associated Extraversion . Openness Experience linked lower number children, more frequent use hormonal contraceptives, first breast examination. Women higher Agreeableness scores less likely contraceptives underwent later life. Conscientiousness increased risk developing who used examinations earlier life, while those had breastfed children chose have mammogram Personality affect health-related behaviors should be taken into account when designing theoretical models as well interventions regarding health habits.

Язык: Английский

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Quality-of-Life Assessment in Patients Undergoing Mastectomy and Breast Reconstruction for Moderate-Penetrance Gene-Related Breast Cancer

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(4), С. 1140 - 1140

Опубликована: Фев. 10, 2025

Background. Breast cancer remains a leading cause of cancer-related death among women, with genetic mutations playing key role. While high-penetrance are well-studied, moderate-to-low-penetrance mutations, which present challenges in clinical decision-making and patient outcomes, less understood. This study explores the quality life breast patients moderate-penetrance focusing on psychosocial physical consequences mastectomy reconstruction to improve patient-centered care. Materials Methods. A cohort 620 treated at Regina Maria Private Health Network, Bucharest, between January 2022 July 2024 was identified. From this group, 61 were selected based following criteria: (1) meeting NCCN testing guidelines, (2) carrying (3) undergoing bilateral double reconstruction, (4) agreeing complete modified version BREAST-Q questionnaire. Genetic performed using 125-gene next-generation sequencing panel. Statistical analyses included non-parametric tests examine group differences correlations. Results. Significant correlations found several factors. Emotional distress positively correlated concerns for family, while couple relationships financial burden showed strong positive association. Negative self-concept. Distress levels varied, "Interference personal relationships" causing more than "Impact employment", distressing impact sexuality. Conclusions. Prophylactic significantly reduces risk women mutations. highlights relationship surgical choices quality-of-life factors, advancing personalized prevention strategies emphasizing

Язык: Английский

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Poly(ADP-ribose) polymerase inhibitors in cancer therapy

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have emerged as critical agents for cancer therapy. By inhibiting the catalytic activity of PARP enzymes and trapping them in DNA, PARPis disrupt DNA repair, ultimately leading to cell death, particularly cells with homologous recombination repair deficiencies, such those harboring BRCA mutations. This review delves into mechanisms action anticancer treatments, including inhibition synthetic lethality, replication stress. Furthermore, clinical applications various cancers their adverse effects well combinations other therapies underlying resistance are summarized. provides comprehensive insights role a particular focus on potential PARPi-based precision medicine treatment.

Язык: Английский

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Beyond the BRCA1/2 genes in ovarian cancer: the role of germline pathogenic variants in the ATM gene

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Фев. 21, 2025

Abstract Background Ovarian Cancer (OC) prevention and early-stage detection represents a challenge due to the lack of effective surveillance. The identification high-risk women is crucial as it provides access prophylactic oophorectomy reduces disease burden. Next-Generation Sequencing approaches enable investigation several genes associated with monogenic hereditary cancer predisposition, including ovarian cancer. For family members patients affected by without germline pathogenic variant, despite increased empirical risk (3 times) incidence, surgery not indicated but may be suggested only efficient strategy. Methods Results We hereby present 2 cases OC in which heterozygous variant ATM gene was identified: first contest Hereditary Breast (HBOC) history and, other one, late onset neoplasms, underline importance defining guidelines management moderate penetrance variants also for prevention. Conclusions Carriers have an neoplasms mostly breast absolute estimated 2–3 times greater than general population. these there well-established evidence benefit reducing bilateral Salpingo-oophorectomy.

Язык: Английский

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