The emerging landscape and future perspective of SCLC transformation: from molecular mechanisms to therapeutic strategies

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер 207, С. 104616 - 104616

Опубликована: Янв. 11, 2025

Язык: Английский

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Exploring lung cancer microenvironment: pathways and nanoparticle-based therapies

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 11, 2025

Язык: Английский

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Recent Research on Role of p53 Family in Small-Cell Lung Cancer

Cancers, Год журнала: 2025, Номер 17(7), С. 1110 - 1110

Опубликована: Март 26, 2025

Small-cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid proliferation, early metastasis, and frequent recurrence, which contribute to poor prognosis. SCLC defined the near-universal inactivation of key tumor suppressor genes, notably TP53 RB1, play central roles in its pathogenesis resistance therapy. The p53 family proteins, including p53, p63, p73, essential maintaining cellular homeostasis suppression. mutations are almost ubiquitous SCLC, leading dysregulated apoptosis cell cycle control. Moreover, p73 shows potential as compensatory mechanism for loss, while p63 has minimal role this type. In review, we explore molecular functional interplay emphasizing members' distinct yet interconnected suppression, immune modulation, therapy resistance. We highlight emerging therapeutic strategies targeting these pathways, reactivating mutant exploiting synthetic lethality, addressing evasion mechanisms. Furthermore, review underscores urgent need novel, isoform-specific interventions enhance treatment efficacy improve patient outcomes challenging disease.

Язык: Английский

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Tumor-Associated Molecules Lead the Way to New Therapies for Small Cell Lung Cancer

JCO Oncology Practice, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Язык: Английский

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Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Май 29, 2025

Cellular senescence exerts dual roles in lung cancer pathogenesis: initially suppressing tumorigenesis via p53/p21/p16-mediated cell cycle arrest, but promoting malignancy through the senescence-associated secretory phenotype (SASP). SASP secretes cytokines, proteases, and growth factors, reshaping tumor microenvironment (TME) to drive immune evasion, metastasis, therapy resistance. NF-κB activation induces APOBEC3B mutagenesis PD-L1 overexpression, while mTOR signaling enhances glycolysis OXPHOS fuel growth. Clinically, telomere attrition, p16/p21 expression, components serve as prognostic biomarkers. Therapeutic strategies target senescent cells SASP. Future directions focus on single-cell multi-omics decode heterogeneity, spatially controlled drug delivery, therapies targeting senescence-immune-metabolic crosstalk. By unraveling senescence’s regulatory mechanisms, this review highlights precision approaches overcome resistance improve outcomes.

Язык: Английский

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p53 Genetics and Biology in Lung Carcinomas: Insights, Implications and Clinical Applications

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1453 - 1453

Опубликована: Июнь 29, 2024

The

Язык: Английский

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RB1 Mutations Induce Smoking‐Related Bladder Cancer by Modulating the Cytochrome P450 Pathway

Environmental Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 6, 2024

Cigarette smoking causes multiple cancers by directly influencing mutation burden of driver mutations. However, the mechanism between somatic caused cigarette and bladder tumorigenesis remains elusive. Smoking-related profile cancer was characterized The Cancer Genome Atlas cohort. Integraticve OncoGenomics database utilized to detect smoking-related genes, its biological predictions were interpreted based on bulk transcriptome single-cell transcriptome, as well cell experiments. associated with an increased tumor mutational under 65 years old (p = 0.031), generated specific signatures in smokers. RB1 identified a differentially mutated gene smokers nonsmokers, rate twofold after 0.008). mutations 4-aminobiphenyl interference could significantly decrease expression level thus promote proliferation, invasion, migration ability cells. Enrichment analysis real-time quantitative PCR (RT-qPCR) data showed that inhibited cytochrome P450 pathway reducing levels UGT1A6 AKR1C2. In addition, we also observed component immunological cells regulated through stronger cell-to-cell interactions epithelial scissor

Язык: Английский

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Comprehensive review of reinforcement learning in lung cancer diagnosis and treatment: Taxonomy, challenges and recommendations

Computers in Biology and Medicine, Год журнала: 2024, Номер 183, С. 109326 - 109326

Опубликована: Окт. 25, 2024

Язык: Английский

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Mixtures of Three Mortaparibs with Enhanced Anticancer, Anti-Migration, and Antistress Activities: Molecular Characterization in p53-Null Cancer Cells

Cancers, Год журнала: 2024, Номер 16(12), С. 2239 - 2239

Опубликована: Июнь 17, 2024

Mortalin, a member of the Hsp70 family proteins, is commonly enriched in many types cancers. It promotes carcinogenesis and metastasis multiple ways which inactivation tumor suppressor activity p53 has been firmly established. The downregulation mortalin and/or disruption mortalin–p53 interactions by small molecules earlier shown to activate function yielding growth arrest/apoptosis cancer cells. Mortaparibs (Mortaparib, MortaparibPlus, MortaparibMild) are chemical inhibitors isolated cell-based two-way screening involving (i) shift staining pattern from perinuclear (characteristics cells) pancytoplasmic normal (ii) nuclear enrichment p53. They have similar structures also cause inhibition PARP1 hence were named Mortaparibs. In present study, we report anticancer anti-metastasis MortaparibMild (4-[(4-amino-5-thiophen-2-yl-1,2,4-triazol-3-yl)sulfanylmethyl]-N-(4-methoxyphenyl)-1,3-thiazol-2-amine) p53-null By extensive molecular analyses cell proliferation, arrest, apoptosis pathways, demonstrate that although it causes relatively weaker cytotoxicity compared Mortaparib its lower concentrations equally potent inhibit migration. We developed combinations (called MortaparibMix-AP, MortaparibMix-AM, MortaparibMix-AS) consisting different ratios three for specifically enhancing their anti-proliferation, anti-migration, antistress activities, respectively. Based on control treated cells, suggest mixtures may be considered further laboratory clinical studies validating use treatment as well prevention relapse metastasis.

Язык: Английский

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Capivasertib augments chemotherapy via Akt inhibition in preclinical small cell lung cancer models

Fundamental and Clinical Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Background Small cell lung cancer (SCLC) is a highly aggressive type of for which platinum‐based chemotherapy the standard care. Despite an initial response to this therapy, patients eventually develop resistance chemotherapy. Objectives To investigate potential capivasertib, approved drug advanced breast cancer, enhance efficacy cisplatin in preclinical SCLC models and explore underlying mechanisms. Methods lines were treated with capivasertib cisplatin, alone or combination, assess viability, proliferation, colony formation, apoptosis. Next, capivasertib's effects, combined evaluated mouse model. Mechanistic studies focused on Akt MYC signaling, constitutively active overexpression used its role. Results Capivasertib against panel regardless cellular origin genetic profiling IC50 at clinically achievable range. Particularly, inhibits proliferation anchorage‐independent formation induces apoptosis cells. It significantly augments cisplatin's inhibitory effects all tested lines. Importantly, non‐toxic dose effective delaying growth mice combination achieves nearly complete tumor inhibition. confirm that furthermore, reversed anti‐SCLC activity capivasertib. Conclusion Our work first reveal inhibition can augment SCLC, useful addition treatment armamentarium SCLC.

Язык: Английский

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