Cisplatin in Liver Cancer Therapy

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10858 - 10858

Опубликована: Июнь 29, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well transarterial chemoembolization (TACE) hepatic arterial infusion (HAIC) are used to treat HCC. TACE HAIC have long been standard of care for patients with HCC but limited treatment intrahepatic lesions. doxorubicin or chemohormonal therapy tamoxifen also considered, neither has demonstrated survival benefits. In HCC, cisplatin administered transhepatic arterially local treatment. Subsequently, cisplatin-refractory cases due drug resistance, a shift systemic different mechanism action expected produce new antitumor effects. Cisplatin tumors other than This review summarizes resistance describes major hepatobiliary cancers which anticancer agent, focus on

Язык: Английский

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SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1

Science Advances, Год журнала: 2024, Номер 10(14)

Опубликована: Апрель 3, 2024

Triple-negative breast cancer (TNBC) is the deadliest subtype of owing to lack effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted progression, as confirmed by cell proliferation, colony formation, transwell migration, invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 ubiquitination-dependent degradation SF3A2, which turn regulated UBR5, thus forming feedback loop balance these two oncoproteins. Moreover, SF3A2 accelerated progression by, at least part, specifically regulating alternative makorin ring finger protein 1 ( MKRN1 ) promoting expression dominant oncogenic isoform, MKRN1-T1 . Furthermore, participated regulation both extrinsic intrinsic apoptosis, leading cisplatin resistance cells. Collectively, findings reveal previously unknown role resistance, highlighting potential target for patients with TNBC.

Язык: Английский

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AMPK–mTOR–Mediated Activation of Autophagy Promotes Formation of Dormant Polyploid Giant Cancer Cells

Cancer Research, Год журнала: 2021, Номер 82(5), С. 846 - 858

Опубликована: Дек. 29, 2021

Dormant cancer cells that survive anticancer therapy can lead to recurrence and disseminated metastases prove fatal in most cases. Recently, specific dormant polyploid giant (PGCC) have drawn our attention because of their association with the clinical risk nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous data. In this study, we report biological properties PGCC, including mitochondrial alterations, reveal autophagy is a critical mechanism PGCC induction. Moreover, pharmacologic or genetic inhibition greatly impaired formation, significantly suppressing metastasis improving survival mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, which then produced low ATP levels activated via AMPK-mTOR pathway promote formation. Analysis transcriptional epigenetic landscape revealed overexpression RIPK1, scaffolding function RIPK1 was required for pathway-induced survival. High numbers PGCCs correlated shorter time worse outcomes patients NPC. Collectively, these findings suggest therapeutic approach targeting cancer.Pretreatment an inhibitor before chemotherapy could prevent formation therapy-induced cells, thereby reducing carcinoma.

Язык: Английский

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Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

Pharmaceutics, Год журнала: 2022, Номер 14(5), С. 954 - 954

Опубликована: Апрель 28, 2022

Countless expectations converge in the multidisciplinary endeavour for search and development of effective safe drugs fighting cancer. Although they still embody a minority pharmacological agents currently clinical use, metal-based complexes have great yet unexplored potential, which probably hides forthcoming anticancer drugs. Following historical success cisplatin congeners, but also taking advantage conventional chemotherapy limitations that emerged with applications clinic, design non-platinum chemotherapeutics, either as or prodrugs, represents rapidly evolving field wherein candidate compounds can be fine-tuned to access interactions druggable biological targets. Moving this direction, over last few decades platinum family metals, e.g., ruthenium palladium, been largely proposed. Indeed, transition metals molecular platforms where originate are endowed unique chemical features based on, not limited to, redox activity coordination geometries, well ligand selection (including their inherent reactivity bioactivity). Herein, current progress chemoth reviewed. Converging on recent literature, new attractive chemotherapeutics other than platinum—and bioactivity mechanisms action—are examined discussed. A special focus is committed ruthenium, rhodium, iridium, gold derivatives, more experimental data nowadays available. Next platinum-based agents, ruthenium-based were first reach stage evaluation humans, opening scenarios alternative chemotherapeutic options treat

Язык: Английский

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Herb–drug interactions between Panax notoginseng or its biologically active compounds and therapeutic drugs: A comprehensive pharmacodynamic and pharmacokinetic review

Journal of Ethnopharmacology, Год журнала: 2023, Номер 307, С. 116156 - 116156

Опубликована: Фев. 6, 2023

Язык: Английский

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PD-1/PD-L1 and DNA Damage Response in Cancer

Cells, Год журнала: 2023, Номер 12(4), С. 530 - 530

Опубликована: Фев. 7, 2023

The application of immunotherapy for cancer treatment is rapidly becoming more widespread. Immunotherapeutic agents are frequently combined with various types treatments to obtain a durable antitumor clinical response in patients who have developed resistance monotherapy. Chemotherapeutic drugs that induce DNA damage and trigger (DDR) an increase the expression programmed death ligand-1 (PD-L1) can be employed by cells avoid immune surveillance. PD-L1 exposed on turn targeted re-establish immune-reactive tumor microenvironment, which ultimately increases tumor’s susceptibility therapies. Here we review recent advances how DDR regulates point out effect etoposide, irinotecan, platinum compounds anti-tumor response.

Язык: Английский

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Molecular mechanisms underlying cisplatin-induced nephrotoxicity and the potential ameliorative effects of essential oils: A comprehensive review

Tissue and Cell, Год журнала: 2024, Номер 88, С. 102377 - 102377

Опубликована: Апрель 6, 2024

Язык: Английский

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Cancer Mutations Converge on a Collection of Protein Assemblies to Predict Resistance to Replication Stress

Cancer Discovery, Год журнала: 2024, Номер 14(3), С. 508 - 523

Опубликована: Янв. 18, 2024

Rapid proliferation is a hallmark of cancer associated with sensitivity to therapeutics that cause DNA replication stress (RS). Many tumors exhibit drug resistance, however, via molecular pathways are incompletely understood. Here, we develop an ensemble predictive models elucidate how mutations impact the response common RS-inducing (RSi) agents. The implement recent advances in deep learning facilitate multidrug prediction and mechanistic interpretation. Initial studies tumor cells identify 41 assemblies integrate alterations hundreds genes for accurate prediction. These cover roles transcription, repair, cell-cycle checkpoints, growth signaling, which 30 shown by loss-of-function genetic screens regulate or restart. model translates cisplatin-treated cervical patients, highlighting RTK-JAK-STAT assembly governing resistance. This study defines compendium mechanisms affect therapeutic responses, implications precision medicine.

Язык: Английский

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Comprehensive multi-omics analyses exposes a precision therapy strategy that targets replication stress in hepatocellular carcinoma using WEE1 inhibition

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(24), С. 15749 - 15749

Опубликована: Дек. 12, 2022

Globally, there are over half a million new patients with head and neck squamous cell carcinomas (HNSCC) every year. The current therapeutic approaches to HNSCC surgery adjuvant radiotherapy. These carry high incidence of metastasis or recurrence from cells' radioresistance. Recent studies have revealed that combination radiosensitizers can be used improve the radioresistance in HNSCC; however, few agents approved as radiosensitizers. constitutive activation phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) pathway is vitally oncogenic type signaling promotes tumorigenesis, metastasis, radiotherapy resistance HNSCC. Pharmacological targeting PI3K/AKT/mTOR considered promising strategy radiosensitization In this review, we summarize significance highlight potential small molecule inhibitors against for treatment. It provides mechanistic framework development drugs via pathway.

Язык: Английский

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