The two sides of chromosomal instability: drivers and brakes in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 29, 2024

Abstract Chromosomal instability (CIN) is a hallmark of cancer and associated with tumor cell malignancy. CIN triggers chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes chromosomes. arises errors DNA replication segregation during division, formation abnormal and/or structure Errors result licensing as well stress, such double-strand breaks stalled forks; meanwhile, stem defects machinery, centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, defective sister chromatids cohesion. In cells, deleterious damage, proteotoxic metabolic alteration, cycle arrest, senescence. Paradoxically, despite these negative consequences, one hallmarks found over 90% solid tumors blood cancers. Furthermore, could endow enhanced adaptation capabilities due increased intratumor heterogeneity, thereby facilitating adaptive resistance therapies; however, excessive induce death, “just-right” model for tumors. Elucidating complex nature crucial understanding dynamics tumorigenesis developing effective anti-tumor treatments. This review provides an overview causes consequences CIN, paradox phenomenon that continues perplex researchers. Finally, this explores potential CIN-based therapy.

Язык: Английский

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Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 29, 2024

Cell death is a fundamental part of life for metazoans. To maintain the balance between cell proliferation and metabolism human bodies, certain number cells need to be removed regularly. Hence, mechanisms have been preserved during evolution multicellular organisms. Tumorigenesis closely related with exceptional inhibition death. Mutations or defects in death-related genes block elimination abnormal enhance resistance malignant chemotherapy. Therefore, investigation enables development drugs that directly induce tumor In guidelines updated by Death Nomenclature Committee (NCCD) 2018, was classified into 12 types according morphological, biochemical functional classification, including intrinsic apoptosis, extrinsic mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, PARP-1 parthanatos, entotic death, NETotic lysosome-dependent autophagy-dependent immunogenic cellular senescence mitotic catastrophe. The mechanistic relationships epigenetic controls cancer progression were previously unclear. this review, we will summarize pathways corresponding regulations. Also, explore extensive interactions these discuss epigenetics which bring benefits therapy.

Язык: Английский

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Dynamics of Spindle Assembly and Position Checkpoints: Integrating Molecular Mechanisms with Computational Models

Computational and Structural Biotechnology Journal, Год журнала: 2025, Номер 27, С. 321 - 332

Опубликована: Янв. 1, 2025

Mitotic checkpoints orchestrate cell division through intricate molecular networks that ensure genomic stability. While experimental research has uncovered key aspects of checkpoint function, the complexity protein interactions and spatial dynamics necessitates computational modeling for a deeper, system-level understanding. This review explores mathematical frameworks-from ordinary differential equations to stochastic simulations, which reveal across multiple scales, encompassing models ranging from simple whole-system simulations with thousands parameters. These approaches have elucidated fundamental properties, including bistable switches driving spindle assembly (SAC) activation, organization principles underlying position (SPOC) signaling, critical features ensuring robustness. study evaluates diverse approaches, rule-based chemical theory, highlighting their successful application in predicting localization patterns response validated live-cell imaging. Contemporary challenges persist integrating temporal refining parameter estimation, enhancing fidelity. However, recent advances single-molecule imaging, data-driven algorithms, machine learning techniques, particularly deep optimization, present transformative opportunities improving model accuracy predictive power. By bridging mechanisms behaviors frameworks, this offers comprehensive perspective on cycle control, practical implications cancer therapeutic development.

Язык: Английский

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Differential cell death pathways in normal and cancerous breast cells response to direct X-ray irradiation and bystander effects

Journal of Radioanalytical and Nuclear Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Язык: Английский

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Regulation of Cell Death: Therapeutic Strategies for Cancer Treatment

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

This chapter explores how to regulate programmed cell death and its relevance in cancer therapy. It points the need of investigate mechanisms death, like apoptosis, necroptosis, and, more recently, exposed ferroptosis, while creating approaches for treatment malignant diseases. In spite progress field targeted therapies, is still a main cause due incapability cells undergo apoptosis. The highlights significance adopting complex that encompass multiple types occurring within both tumor microenvironment. Of note are functions oncogenes suppressor genes regulation cellular processes, specific role apoptosis formation process, possibility increase neoplastic cells. There metastasis critical such as TP53 gene, along with presence an over expression anti-apoptotic proteins. Examples this would include Bcl-2 IAPs, which protect against stimuli required death. immunotherapy combination therapies described emerging strategies enhance efficacy treatments. document also deals problem resistance induction necessity further clinical studies new therapeutic agents practice. summary, it diversity biology paradigm shift achieve

Язык: Английский

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Polyphenol-based pH-responsive nanoparticles enhance chemo-immunotherapy in pancreatic cancer

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 615 - 629

Опубликована: Фев. 16, 2025

Язык: Английский

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Phosphocreatine promotes epigenetic reprogramming to facilitate glioblastoma growth through stabilizing BRD2

Cancer Discovery, Год журнала: 2024, Номер 14(8), С. 1547 - 1565

Опубликована: Апрель 1, 2024

Glioblastoma (GBM) exhibits profound metabolic plasticity for survival and therapeutic resistance, while the underlying mechanisms remain unclear. Here, we show that GBM stem cells reprogram epigenetic landscape by producing substantial amounts of phosphocreatine (PCr). This production is attributed to elevated transcription brain-type creatine kinase, mediated Zinc finger E-box binding homeobox 1. PCr inhibits poly-ubiquitination chromatin regulator bromodomain containing protein 2 (BRD2) outcompeting E3 ubiquitin ligase SPOP BRD2 binding. Pharmacological disruption biosynthesis cyclocreatine (cCr) leads degradation a decrease in its targets' transcription, which chromosome segregation cell proliferation. Notably, treatment significantly impedes tumor growth sensitizes tumors inhibitor mouse models without detectable side effects. These findings highlight high druggable feature promising target treatment. Significance: an adaptable metabolism crucial therapy resistance. We demonstrate modify their epigenetics (PCr), prevents promotes accurate segregation. Disrupting improves efficacy inhibitors models.

Язык: Английский

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Inhibiting autophagy enhanced mitotic catastrophe-mediated anticancer immune responses by regulating the cGAS-STING pathway

Cancer Letters, Год журнала: 2024, Номер 586, С. 216695 - 216695

Опубликована: Фев. 5, 2024

Язык: Английский

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Nanomedicine-induced programmed cell death in cancer therapy: mechanisms and perspectives

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Авг. 29, 2024

The balance of programmed cell death (PCD) mechanisms, including apoptosis, autophagy, necroptosis and others, is pivotal in cancer progression treatment. Dysregulation these pathways results uncontrolled growth resistance to conventional therapies. Nanomedicine offers a promising solution oncology through targeted drug delivery enabling precise targeting cells while preserving healthy tissues. This approach reduces the side effects traditional chemotherapy enhances treatment efficacy by engaging PCD pathways. We details each pathway, their innovative nanomedicine strategies activate pathways, thereby enhancing therapeutic specificity minimizing harm precision nanotechnology promises significant improvements outcomes. synergy between activation could lead more effective less toxic therapies, heralding new era

Язык: Английский

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Novel Quinolin-4-ylcarbonylhydrazine Having N-(3-Arylacryloyl) Moiety: Design, Synthesis and Biological Evaluation as Potential Cytotoxic Agents against MDA-MB-231 via Tubulin Assembly Inhibition

Journal of Molecular Structure, Год журнала: 2024, Номер 1321, С. 140214 - 140214

Опубликована: Сен. 27, 2024

Язык: Английский

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