Hallmarks of DNA replication stress

Molecular Cell, Год журнала: 2022, Номер 82(12), С. 2298 - 2314

Опубликована: Июнь 1, 2022

Язык: Английский

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Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1263 - 1263

Опубликована: Янв. 19, 2024

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision replication for fast proliferation and increased genomic instability. To overcome the consequences improper control, malignant frequently inactivate parts their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other which help maintain fork stability (ATR-CHK1). This creates dependency remaining DDR pathways, vulnerability further destabilization synthetic lethality inhibitors with common oncogenic alterations such mutations TP53, RB1, ATM, amplifications MYC, CCNE1 others. The RS normally limited by coordination cell cycle, transcription replication. Inhibition WEE1 PKMYT1 kinases, prevent unscheduled mitosis entry, leads fragility under-replicated sites. Recent evidence also shows that inhibition Cyclin-dependent kinases (CDKs), CDK4/6, CDK2, CDK8/19 CDK12/13 can contribute through disruption repair control. Here, we review main causes in cancers well therapeutic targets—ATR, CHK1, PARP inhibitors.

Язык: Английский

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Context-dependent role of SIRT3 in cancer

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(2), С. 173 - 190

Опубликована: Янв. 19, 2024

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Cyclin-dependent protein kinases and cell cycle regulation in biology and disease

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 12, 2025

Abstract Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified as kinases able drive division. In reality, human genome contains 20 different CDKs, which can be divided in at least three sub-family with functions, mechanisms regulation, expression patterns and subcellular localization. Most these play fundamental roles normal physiology eucaryotic cells; therefore, their deregulation is associated onset and/or progression multiple disease including but not limited neoplastic neurodegenerative conditions. Here, we describe functions categorized into main functional groups they classified, highlighting most relevant pathways that functions. We then discuss potential CDKs pathologies, a particular focus on cancer, have extensively studied explored therapeutic targets. Finally, how inhibitors become standard therapies selected cancers propose novel ways investigation export targeting from cancer other chronic diseases. hope effort made collecting all available information both prominent lesser-known CDK family members will help identify develop areas research improve lives patients affected by debilitating

Язык: Английский

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Calycosin reduces myocardial fibrosis and improves cardiac function in post-myocardial infarction mice by suppressing TGFBR1 signaling pathways

Phytomedicine, Год журнала: 2022, Номер 104, С. 154277 - 154277

Опубликована: Июнь 15, 2022

Язык: Английский

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Interplay between LncRNAs and microRNAs in Breast Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8095 - 8095

Опубликована: Апрель 30, 2023

(1) Although long noncoding RNAs (lncRNAs) are known to be precursors of microRNAs (miRNAs), they frequently act as competing endogoneous (ceRNAs), yet still their interplay with miRNA is not well known. However, interaction miRNAs may result in the modulation action. (2) To determine contribution these RNA molecules tumor resistance chemotherapeutic drugs, it essential consider only oncogenic and suppressive function but also impact lncRNAs on miRNAs. Therefore, we performed an extensive search different databases including PubMed. (3) The present study concerns between regulatory post-transcriptional network drugs used treatment breast cancer. (4) Consideration this improve for new circumvent chemoresistance.

Язык: Английский

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The pathophysiology of the cell cycle in cancer and treatment strategies using various cell cycle checkpoint inhibitors

Pathology - Research and Practice, Год журнала: 2023, Номер 251, С. 154854 - 154854

Опубликована: Окт. 4, 2023

Язык: Английский

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Comprehensive proteogenomic characterization of rare kidney tumors

Cell Reports Medicine, Год журнала: 2024, Номер 5(5), С. 101547 - 101547

Опубликована: Май 1, 2024

Non-clear cell renal carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis aggressive disease, therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, metabolic aberrations in RCC subtypes. RCCs high genome instability display overexpression IGF2BP3 PYCR1. Integration single-cell bulk transcriptome data predicts cell-of-origin clarifies subtype-specific proteogenomic signatures. Expression biomarkers MAPRE3, ADGRF5, GPNMB differentiates oncocytoma from chromophobe RCC, PIGR SOSTDC1 distinguish papillary MTSCC. This study expands our knowledge signatures, potential non-ccRCC.

Язык: Английский

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Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression

Cancer Drug Resistance, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

This review offers an expert perspective on biomarkers, CDK4/6 inhibitor efficacy, and therapeutic approaches for managing hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-) advanced breast cancer (ABC), particularly after progression. Key trials have demonstrated that combining inhibitors with endocrine therapy (ET) significantly improves progression-free survival (PFS), median durations ranging from 14.8 to 26.7 months, overall (OS), reaching up 53.7 months. Actionable such as PIK3CA ESR1 mutations, emerged pivotal tools guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib elacestrant emphasizing important role biomarkers in guiding selection therapy. overview aims provide clinicians a practical up-to-date framework inform decisions improve patient care context this challenging disease. Additionally, we emerging novel strategies address difficult clinical landscape.

Язык: Английский

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Cancer cell cycle dystopia: heterogeneity, plasticity, and therapy

Trends in cancer, Год журнала: 2022, Номер 8(9), С. 711 - 725

Опубликована: Май 20, 2022

Язык: Английский

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