Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer

Life, Год журнала: 2025, Номер 15(1), С. 126 - 126

Опубликована: Янв. 18, 2025

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations environmental stressors, on one hand, cancer cell structure, functioning, behavior. Aberrant PTMs can be considered as enabling characteristics long they orchestrate all malignant variability in proteome cells, cancer-associated tumor microenvironment (TME). On other enhance anticancer mechanisms tumoral ecosystem or sustain beneficial effects oncologic therapies through degradation inactivation carcinogenic or/and activation tumor-suppressor proteins. In this review, we summarized analyzed a wide spectrum involved regulatory that drive tumorigenesis, genetic instability, epigenetic reprogramming, events metastatic cascade, cytoskeleton extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, metabolism rewiring most important hallmarks cancer. All develop due to proteins, which modulate gene transcription, intracellular signaling, protein size, activity, stability localization, trafficking, secretion, half-life, protein–protein interactions (PPIs). associated with exploited better understand underlying molecular heterogeneous chameleonic disease, find new biomarkers progression prognosis, personalize oncotherapies, discover targets for drug development.

Язык: Английский

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Duplexed CeTEAM drug biosensors reveal determinants of PARP inhibitor selectivity in cells

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108361 - 108361

Опубликована: Фев. 1, 2025

Язык: Английский

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PARP inhibitors in ovarian cancer: mechanisms of resistance and implications to therapy

DNA repair, Год журнала: 2025, Номер unknown, С. 103830 - 103830

Опубликована: Апрель 1, 2025

Advanced epithelial ovarian cancer of the high-grade serous subtype (HGSOC) remains a significant clinical challenge due to development resistance current platinum-based chemotherapies. PARP1/2 inhibitors (PARPi) exploit well-characterised homologous recombination repair deficiency (HRD) in HGSOC and offer an effective targeted approach treatment. Several trials demonstrated that PARPi (olaparib, rucaparib, niraparib) significantly improved progression-free survival (PFS) recurrent maintenance setting. However, 40-70 % patients develop Resistance presenting ongoing clinic. Therefore, there is unmet need for novel therapies biomarkers identify intrinsic or acquired cancer. Understanding mechanisms crucial identifying molecular vulnerabilities, developing patient stratification guiding treatment decisions. Here, we summarise landscape associated with such as restored functionality, replication fork stability alterations PARP1 PARP2 DNA damage response. We highlight role circulating tumour (ctDNA) its potential 'real-time' Moreover, explore other innovative strategies aimed at overcoming specific mechanisms, including inhibition ATR, WEE1 POLQ. also examine rechallenge resistance.

Язык: Английский

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PARG inhibition induces nuclear aggregation of PARylated PARP1

Structure, Год журнала: 2024, Номер 32(11), С. 2083 - 2093.e5

Опубликована: Окт. 14, 2024

Язык: Английский

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